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Original Articles
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Revisiting human sparganosis: a pathologic review from a single institution
Jeemin Yim, Young A Kim, Jeong Hwan Park, Hye Eun Park, Hyun Beom Song, Ji Eun Kim
J Pathol Transl Med. 2026;60(1):83-91.   Published online January 9, 2026
DOI: https://doi.org/10.4132/jptm.2025.10.14
  • 1,716 View
  • 95 Download
AbstractAbstract PDF
Background
Sparganosis is a rare parasitic infection caused by Spirometra species. Although it was relatively common in the past, it is now often overlooked. In this study, we review cases diagnosed through histopathological examination at a single institution in recent years to raise awareness of this neglected parasitic disease. Methods: We retrospectively analyzed cases of human sparganosis identified in the pathology archives of a single institution in South Korea between 2004 and 2025. A comprehensive review was conducted, including demographic data, clinical features, lesion locations, imaging findings, exposure history (such as dietary habits), and histopathologic findings. Results: A total of 15 patients were identified, including 10 females and 5 males, with a mean age of 65.1 years. Lesions were most commonly located in the lower extremities and breast. Imaging findings were largely nonspecific, with ultrasonography being the most frequently used modality. In most cases, clinical suspicion of sparganosis was absent, and excision was performed under the impression of a benign or malignant tumor. Histologically, variably degenerated parasitic structures were identified within granulomatous inflammation. However, preserved features such as calcospherules and tegumental structures facilitated definitive diagnosis. Conclusions: This study underscores the importance of recognizing the characteristic histopathological features of sparganosis, which can allow for accurate diagnosis even in the absence of clinical suspicion. Although rare, sparganosis remains a relevant diagnostic consideration in endemic regions, particularly in East Asia.
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Diagnostic value of cytology in detecting human papillomavirus–independent cervical malignancies: a nation-wide study in Korea
Hye-Ra Jung, Junyoung Shin, Chong Woo Yoo, Eun Na Kim, Cheol Lee, Kyeongmin Kim, Ho-chang Lee, Yonghee Lee, Ji Hye Kim, Soo Jin Jung, Yumin Chung, Joo Yeon Kim, Hye Eun Park, Tae Hoen Kim, Wonae Lee, Min-Sun Cho, Ran Hong, Yoon Jung Choi, Younghee Choi, Young Sub Lee, Sang-Ryung Lee, Myunghee Kang, Young Jin Seo, Seung-Sook Lee, Yoon-Jung Hwang, Hyun-Jung Kim
J Pathol Transl Med. 2025;59(6):444-452.   Published online November 11, 2025
DOI: https://doi.org/10.4132/jptm.2025.10.21
  • 4,225 View
  • 140 Download
AbstractAbstract PDF
Background
Human papillomavirus (HPV) independent cervical malignancies (HPV-IDCMs) have recently been classified by the World Health Organization (WHO) 5th edition. These malignancies have historically received limited attention due to their rarity and the potential for evasion of HPV-based screening.
Methods
We retrospectively reviewed 5,854 biopsy-confirmed cervical malignancies from 22 institutions over 3 years (July 2020–June 2023). Histologic classification followed the WHO guidelines. HPV independence was confirmed by dual negativity for p16 and HPV; discordant cases (p16-positive/HPV-negative) underwent additional HPV testing using paraffin-embedded tissue. Cytological results were matched sequentially to histological confirmation.
Results
The prevalence of HPV-IDCM was 4.4% (257/5,854) overall and was 3.6% (208/5,805 cases) among primary cervical malignancy. Patient age of HPV-IDCM was 29 to 89 years (median, 57.79). Its histologic subtypes included primary adenocarcinoma (n = 116), endometrial adenocarcinoma (n = 35), squamous cell carcinoma (n = 72), metastatic carcinoma (n = 14), carcinoma, not otherwise specified (n = 10), neuroendocrine carcinoma (n = 3), and others (n = 7). Among 155 cytology-histological matched cases, the overall and primary Pap test detection rates were 85.2% (132/155) and 83.2% (104/125), respectively. The interval between cytology and histologic confirmation extended up to 38 months.
Conclusions
HPV-IDCMs comprised 3.6% of primary cervical malignancies with a high detection rate via cytology (83.2%). These findings affirm the value of cytological screening, particularly in patients with limited screening history or at risk for HPV-independent lesions, and may guide future screening protocols.
Review Article
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Central nervous system tumors with BCOR internal tandem duplications: a systematic review of clinical, radiological, and pathological features in 69 cases
Ji Young Lee, Sung Sun Kim, Hee Jo Baek, Tae-Young Jung, Kyung-Sub Moon, Jae-Hyuk Lee, Kyung-Hwa Lee
J Pathol Transl Med. 2025;59(5):273-280.   Published online September 1, 2025
DOI: https://doi.org/10.4132/jptm.2025.07.23
  • 4,009 View
  • 189 Download
AbstractAbstract PDFSupplementary Material
Central nervous system tumors with BCL6 corepressor (BCOR) internal tandem duplications (ITDs) constitute a rare, recently characterized pediatric neoplasm with distinct molecular and histopathological features. To date, 69 cases have been documented in the literature, including our institutional case. These neoplasms predominantly occur in young children, with the cerebellum representing the most frequent anatomical location. Radiologically, these tumors present as large, well-circumscribed masses frequently demonstrating necrosis, hemorrhage, and heterogeneous enhancement. Histologically, they are characterized by a monomorphic cellular population featuring ependymoma-like perivascular pseudorosettes, myxoid stroma, and elevated mitotic activity. Immunohistochemically, these tumors exhibit sparse glial fibrillary acidic protein expression while consistently demonstrating positive staining for vimentin and CD56. The defining molecular hallmark is a heterozygous ITD within exon 15 of the BCOR gene, with insertions ranging from 9 to 42 amino acids in length. BCOR immunohistochemistry reveals nuclear positivity in 97.9% of examined cases, although this finding is not pathognomonic for BCOR ITDs. This comprehensive review synthesizes data from all published cases of this novel tumor entity, providing a detailed analysis of clinical presentation, neuroimaging findings, histopathological features with differential diagnostic considerations, therapeutic approaches, and prognostic outcomes.
Original Articles
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Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea
Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho
J Pathol Transl Med. 2023;57(3):166-177.   Published online May 10, 2023
DOI: https://doi.org/10.4132/jptm.2023.04.12
  • 6,669 View
  • 172 Download
  • 6 Web of Science
  • 5 Crossref
AbstractAbstract PDFSupplementary Material
Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Citations

Citations to this article as recorded by  
  • Management of squamous cell carcinoma of unknown primary in the head and neck: current evidence-based diagnostic and treatment strategies
    Marcel Kloppenburg, Matthias Santer, Lukas Schmutzler, Felix Johnson, Benedikt Hofauer, Teresa Steinbichler
    memo - Magazine of European Medical Oncology.2026; 19(1): 45.     CrossRef
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    Christina Sauter, Matthias Sand, Karim Plath, Michaela Maria Plath
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  • Unlocking the Hidden: Advancing Imaging Techniques in Diagnosing Cancers of Unknown Primary in the Head and Neck Region
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  • Characterization of undifferentiated carcinoma of the salivary gland: clinicopathological and immunohistochemical analyses in comparison with lymphoepithelial carcinoma
    Sangjoon Choi, Gyuheon Choi, Hee Jin Lee, Joon Seon Song, Yoon Se Lee, Seung-Ho Choi, Kyung-Ja Cho
    Journal of Pathology and Translational Medicine.2025; 59(6): 361.     CrossRef
  • Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
    Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
    Cancer Immunology, Immunotherapy.2024;[Epub]     CrossRef
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Evaluation of human papillomavirus (HPV) prediction using the International Endocervical Adenocarcinoma Criteria and Classification system, compared to p16 immunohistochemistry and HPV RNA in-situ hybridization
Hezhen Ren, Jennifer Pors, Christine Chow, Monica Ta, Simona Stolnicu, Robert Soslow, David Huntsman, Lynn Hoang
J Pathol Transl Med. 2020;54(6):480-488.   Published online August 31, 2020
DOI: https://doi.org/10.4132/jptm.2020.07.18
  • 8,912 View
  • 175 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDF
Background
The International Endocervical Adenocarcinoma Criteria and Classification (IECC) separated endocervical adenocarcinomas into human papillomavirus (HPV) associated (HPVA) and non–HPV-associated (NHPVA) categories by morphology alone. Our primary objective was to assess the accuracy of HPV prediction by the IECC system compared to p16 immunohistochemistry and HPV RNA in-situ hybridization (RISH). Our secondary goal was to directly compare p16 and HPV RISH concordance.
Methods
Cases were classified by IECC and stained for p16 and HPV RISH on tissue microarray, with discordant p16/HPV RISH cases re-stained on whole tissue sections. Remaining discordant cases (p16/HPV, IECC/p16, IECC/HPV discordances) were re-reviewed by the original pathologists (n = 3) and external expert pathologists (n = 2) blinded to the p16 and HPV RISH results. Final IECC diagnosis was assigned upon independent agreement between all reviewers.
Results
One hundred and eleven endocervical adenocarcinomas were classified originally into 94 HPVA and 17 NHPVA cases. p16 and HPV RISH was concordant in 108/111 cases (97%) independent of the IECC. HPV RISH and p16 was concordant with IECC in 103/111 (93%) and 106/111 (95%), respectively. After expert review, concordance improved to 107/111 (96%) for HPV RISH. After review of the eight discordant cases, one remained as HPVA, four were reclassified to NHPVA from HPVA, two were unclassifiable, and one possibly represented a mixed usual and gastric-type adenocarcinoma.
Conclusions
p16 and HPV RISH have excellent concordance in endocervical adenocarcinomas, and IECC can predict HPV status in most cases. Focal apical mitoses and apoptotic debris on original review led to the misclassification of several NHPVA as HPVA.

Citations

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    Simona Stolnicu
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    Natalie Banet, Karen L. Talia
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    Linghui Lu, Tianqi Liu, Shunni Wang, Jing Li, Feiran Zhang, Yan Ning, Yiqin Wang
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    Simona Stolnicu, Douglas Allison, Aaron M. Praiss, Basile Tessier-Cloutier, Amir Momeni Boroujeni, Jessica Flynn, Alexia Iasonos, Rene Serrette, Lien Hoang, Andrei Patrichi, Cristina Terinte, Anna Pesci, Claudia Mateoiu, Ricardo R. Lastra, Takako Kiyokawa
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  • Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System
    Máire A. Duggan, Qiuli Duan, Ruth M. Pfeiffer, Mary Anne Brett, Sandra Lee, Mustapha Abubakar, Martin Köbel, Monica Rodriguez, Aylin Sar
    Applied Immunohistochemistry & Molecular Morphology.2022; 30(2): 91.     CrossRef
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    Ha Young Woo, Hyun-Soo Kim
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    Simona Stolnicu, Lien Hoang, Noorah Almadani, Louise De Brot, Glauco Baiocchi, Graziele Bovolim, Maria Jose Brito, Georgia Karpathiou, Antonio Ieni, Esther Guerra, Takako Kiyokawa, Pavel Dundr, Carlos Parra-Herran, Sofia Lérias, Ana Felix, Andres Roma, An
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  • Reproducibility of Morphologic Parameters of the International Endocervical Adenocarcinoma Criteria and Classification System and Correlation With Clinicopathologic Parameters: A Multi-Institutional Study
    Pinar Bulutay, Nihan Haberal, Özlem Özen, Özlem Erdem, Emine H. Zeren, İbrahim Kulac, Çagatay Taskiran, Dogan Vatansever, Ali Ayhan, Nilgün Kapucuoğlu
    International Journal of Gynecological Pathology.2022; 41(5): 447.     CrossRef
  • HPV-Negative Cervical Cancer: A Narrative Review
    Francesca Arezzo, Gennaro Cormio, Vera Loizzi, Gerardo Cazzato, Viviana Cataldo, Claudio Lombardi, Giuseppe Ingravallo, Leonardo Resta, Ettore Cicinelli
    Diagnostics.2021; 11(6): 952.     CrossRef
  • International Endocervical Adenocarcinoma Criteria and Classification (IECC): An Independent Cohort With Clinical and Molecular Findings
    Hezhen Ren, Noorah Almadani, Jennifer Pors, Samuel Leung, Julie Ho, Christine Chow, Monica Ta, Kay J. Park, Simona Stolnicu, Robert Soslow, David Huntsman, Blake C. Gilks, Lynn Hoang
    International Journal of Gynecological Pathology.2021; 40(6): 533.     CrossRef
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Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas
Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
J Pathol Transl Med. 2020;54(5):411-418.   Published online July 21, 2020
DOI: https://doi.org/10.4132/jptm.2020.06.22
  • 12,759 View
  • 188 Download
  • 23 Web of Science
  • 25 Crossref
AbstractAbstract PDF
Background
High-risk (HR) human papillomavirus (HPV) is found in a subset of head and neck (HN) squamous cell carcinomas (SCCs). For oropharyngeal SCCs, HR HPV positivity is known to be associated with good prognosis, and a separate staging system for HPV-associated carcinomas using p16 immunohistochemistry (IHC) as a surrogate test has been adopted in the 8th American Joint Committee on Cancer staging system. We examined the HR HPV status and the genotype distribution in five HN subsites.
Methods
Formalin-fixed paraffin-embedded tissue sections were used for p16 IHC and DNA extraction. HPV DNA detection and genotyping were done employing either a DNA chip-based or real-time polymerase chain reaction–based method.
Results
During 2011–2019, a total of 466 SCCs were tested for HPV DNA with 34.1% positivity for HR HPV. Among HN subsites, the oropharynx showed the highest HR HPV prevalence (149/205, 75.1%), followed by the sinonasal tract (3/14, 21.4%), larynx (5/43, 11.6%), hypopharynx (1/38, 2.6%), and oral cavity (1/166, 0.6%). The most common HPV genotype was HPV16 (84.3%) followed by HPV35 (6.9%) and HPV33 (4.4%). Compared with HR HPV status, the sensitivity and specificity of p16 IHC were 98.6% and 94.3% for the oropharynx, and 99.2% and 93.8% for the tonsil, respectively.
Conclusions
Using a Korean dataset, we confirmed that HR HPV is most frequently detected in oropharyngeal SCCs. p16 positivity showed a good concordance with HR HPV DNA for oropharyngeal and especially tonsillar carcinomas. The use of p16 IHC may further be extended to predict HR HPV positivity in sinonasal tract SCCs.

Citations

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Article image
Gene variant profiles and tumor metabolic activity as measured by FOXM1 expression and glucose uptake in lung adenocarcinoma
Ashley Goodman, Waqas Mahmud, Lela Buckingham
J Pathol Transl Med. 2020;54(3):237-245.   Published online March 4, 2020
DOI: https://doi.org/10.4132/jptm.2020.02.08
  • 7,523 View
  • 120 Download
  • 2 Web of Science
  • 1 Crossref
AbstractAbstract PDF
Background
Cancer cells displaying aberrant metabolism switch energy production from oxidative phosphorylation to glycolysis. Measure of glucose standardized uptake value (SUV) by positron emission tomography (PET), used for staging of adenocarcinoma in high-risk patients, can reflect cellular use of the glycolysis pathway. The transcription factor, FOXM1 plays a role in regulation of glycolytic genes. Cancer cell transformation is driven by mutations in tumor suppressor genes such as TP53 and STK11 and oncogenes such as KRAS and EGFR. In this study, SUV and FOXM1 gene expression were compared in the background of selected cancer gene mutations.
Methods
Archival tumor tissue from cases of lung adenocarcinoma were analyzed. SUV was collected from patient records. FOXM1 gene expression was assessed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Gene mutations were detected by allele-specific PCR and gene sequencing.
Results
SUV and FOXM1 gene expression patterns differed in the presence of single and coexisting gene mutations. Gene mutations affected SUV and FOXM1 differently. EGFR mutations were found in tumors with lower FOXM1 expression but did not affect SUV. Tumors with TP53 mutations had increased SUV (p = .029). FOXM1 expression was significantly higher in tumors with STK11 mutations alone (p < .001) and in combination with KRAS or TP53 mutations (p < .001 and p = .002, respectively).
Conclusions
Cancer gene mutations may affect tumor metabolic activity. These observations support consideration of tumor cell metabolic state in the presence of gene mutations for optimal prognosis and treatment strategy.

Citations

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  • Prognostic value of combining clinical factors, 18F-FDG PET-based intensity, volumetric features, and deep learning predictor in patients with EGFR-mutated lung adenocarcinoma undergoing targeted therapies: a cross-scanner and temporal validation study
    Kun-Han Lue, Yu-Hung Chen, Sung-Chao Chu, Chih-Bin Lin, Tso-Fu Wang, Shu-Hsin Liu
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Article image
Colorectal epithelial neoplasm associated with gut-associated lymphoid tissue
Yo Han Jeon, Ji Hyun Ahn, Hee Kyung Chang
J Pathol Transl Med. 2020;54(2):135-145.   Published online January 29, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.06
  • 10,265 View
  • 257 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDF
Background
Colorectal epithelial neoplasm extending into the submucosal gut-associated lymphoid tissue (GALT) can cause difficulties in the differential diagnosis. Regarding GALT-associated epithelial neoplasms, a few studies favor the term “GALT carcinoma” while other studies have mentioned the term “GALT-associated pseudoinvasion/epithelial misplacement (PEM)”.
Methods
The clinicopathologic characteristics of 11 cases of colorectal epithelial neoplasm associated with submucosal GALT diagnosed via endoscopic submucosal dissection were studied.
Results
Eight cases (72.7%) were in males. The median age was 59 years, and age ranged from 53 to 73. All cases had a submucosal tumor component more compatible with GALT-associated PEM. Eight cases (72.7%) were located in the right colon. Ten cases (90.9%) had a non-protruding endoscopic appearance. Nine cases (81.8%) showed continuity between the submucosal and surface adenomatous components. Nine cases showed (81.8%) focal defects or discontinuation of the muscularis mucosae adjacent to the submucosal GALT. No case showed hemosiderin deposits in the submucosa or desmoplastic reaction. No case showed single tumor cells or small clusters of tumor cells in the submucosal GALT. Seven cases (63.6%) showed goblet cells in the submucosa. No cases showed oncocytic columnar cells lining submucosal glands.
Conclusions
Our experience suggests that pathologists should be aware of the differential diagnosis of GALT-associated submucosal extension by colorectal adenomatous neoplasm. Further studies are needed to validate classification of GALT-associated epithelial neoplasms.

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Article image
Comparison of papanicolaou smear and human papillomavirus (HPV) test as cervical screening tools: can we rely on HPV test alone as a screening method? An 11-year retrospective experience at a single institution
Myunghee Kang, Seung Yeon Ha, Hyun Yee Cho, Dong Hae Chung, Na Rae Kim, Jungsuk An, Sangho Lee, Jae Yeon Seok, Juhyeon Jeong
J Pathol Transl Med. 2020;54(1):112-118.   Published online January 15, 2020
DOI: https://doi.org/10.4132/jptm.2019.11.29
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AbstractAbstract PDF
Background
The decrease in incidence of cervical dysplasia and carcinoma has not been as dramatic as expected with the development of improved research tools and test methods. The human papillomavirus (HPV) test alone has been suggested for screening in some countries. The National Cancer Screening Project in Korea has applied Papanicolaou smears (Pap smears) as the screening method for cervical dysplasia and carcinoma. We evaluated the value of Pap smear and HPV testing as diagnostic screening tools in a single institution.
Methods
Patients co-tested with HPV test and Pap smear simultaneously or within one month of each other were included in this study. Patients with only punch biopsy results were excluded because of sampling errors. A total of 999 cases were included, and the collected reports encompassed results of smear cytology, HPV subtypes, and histologic examinations.
Results
Sensitivity and specificity of detecting high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were higher for Pap smears than for HPV tests (sensitivity, 97.14%; specificity, 85.58% for Pap smears; sensitivity, 88.32%; specificity, 54.92% for HPV tests). HPV tests and Pap smears did not differ greatly in detection of low-grade squamous intraepithelial lesion (85.35% for HPV test, 80.31% for Pap smears). When atypical glandular cells were noted on Pap smears, the likelihood for histologic diagnosis of adenocarcinoma following Pap smear was higher than that of high-risk HPV test results (18.8 and 1.53, respectively).
Conclusions
Pap smears were more useful than HPV tests in the diagnosis of HSIL, SCC, and glandular lesions.

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Article image
Analysis of the molecular subtypes of preoperative core needle biopsy and surgical specimens in invasive breast cancer
Ye Sul Jeong, Jun Kang, Jieun Lee, Tae-Kyung Yoo, Sung Hun Kim, Ahwon Lee
J Pathol Transl Med. 2020;54(1):87-94.   Published online November 13, 2019
DOI: https://doi.org/10.4132/jptm.2019.10.14
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AbstractAbstract PDF
Background
Accurate molecular classification of breast core needle biopsy (CNB) tissue is important for determining neoadjuvant systemic therapies for invasive breast cancer. The researchers aimed to evaluate the concordance rate (CR) of molecular subtypes between CNBs and surgical specimens.
Methods
This study was conducted with invasive breast cancer patients who underwent surgery after CNB at Seoul St. Mary’s Hospital between December 2014 and December 2017. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki67 were analyzed using immunohistochemistry. ER and PR were evaluated by Allred score (0–8). HER2 was graded from 0 to +3, and all 2+ cases were reflex tested with silver in situ hybridization. The labeling index of Ki67 was counted by either manual scoring or digital image analysis. Molecular subtypes were classified using the above surrogate markers.
Results
In total, 629 patients were evaluated. The CRs of ER, PR, HER2, and Ki67 were 96.5% (kappa, 0.883; p<.001), 93.0% (kappa, 0.824; p<.001), 99.7% (kappa, 0.988; p<.001), and 78.7% (kappa, 0.577; p<.001), respectively. Digital image analysis of Ki67 in CNB showed better concordance with Ki67 in surgical specimens (CR, 82.3%; kappa, 0.639 for digital image analysis vs. CR, 76.2%; kappa, 0.534 for manual counting). The CRs of luminal A, luminal B, HER2, and triple negative types were 89.0%, 70.0%, 82.9%, and 77.2%, respectively.
Conclusions
CNB was reasonably accurate for determining ER, PR, HER2, Ki67, and molecular subtypes. Using digital image analysis for Ki67 in CNB produced more accurate molecular classifications.

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Review
Current Status of and Perspectives on Cervical Cancer Screening in Korea
Sung-Chul Lim, Chong Woo Yoo
J Pathol Transl Med. 2019;53(4):210-216.   Published online May 16, 2019
DOI: https://doi.org/10.4132/jptm.2019.04.11
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AbstractAbstract PDF
Since the introduction of the Papanicolaou (Pap) smear system in 1943, cervicovaginal cytology has been used as a standard screening test for cervical cancer. The dissemination of this test contributed to reductions of the incidence and mortality of cervical cancer worldwide. In Korea, regular health check-ups for industrial workers and their family members were introduced in 1988 and were performed as part of the National Cancer Screening Program in 1999. As a result, the incidence of cervical cancer in Korea has been steadily decreasing. However, about 800 cases of cervical cancer-related deaths are reported each year due to false-negative test results. Hence, new screening methods have been proposed. Liquid-based cytology (LBC) was introduced in 1996 to overcome the limitations of conventional Pap smears. Since then, other LBC methods have been developed and utilized, including the human papilloma virus test—a method with higher sensitivity that requires fewer screenings. In this study, we review current issues and future perspectives related to cervical cancer screening in Korea.

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Original Article
Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung
Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung
J Pathol Transl Med. 2019;53(2):86-93.   Published online January 14, 2019
DOI: https://doi.org/10.4132/jptm.2018.12.26
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AbstractAbstract PDF
Background
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
Conclusions
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.

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Review
Let Archived Paraffin Blocks Be Utilized for Research with Waiver of Informed Consent
Yong-Jin Kim, Jeong Sik Park, Karam Ko, Chang Rok Jeong
J Pathol Transl Med. 2018;52(3):141-147.   Published online April 5, 2018
DOI: https://doi.org/10.4132/jptm.2018.02.07
  • 10,962 View
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AbstractAbstract PDF
Advances in biomedical and genetic research have contributed to more effective public health improvement via bench-to-bed research and the emergence of personalized medicine. This has certainly showcased the importance of archived human tissues, especially paraffin-embedded blocks in pathology. Currently in Korea, undue legislative regulations of the Bioethics and Safety Act suspend and at times discourage studies from taking place. In this paper, the authors underline the value of paraffin blocks in the era of personalized and translational medicine. We discuss detailed clauses regarding the applicability of paraffin blocks from a legal perspective and compare Korea’s regulations with those of other countries. The necessity for allowing waived consent and Institutional Review Board (IRB) approval will be argued throughout. The authors suggest that researchers declare the following to obtain IRB approval and waiver of informed consents: research could not be practically carried out without a waiver of consent; the proposed research presents no more than minimal risk of harm to subjects, and the waiver of consent will not adversely affect the rights and welfare of subjects; and research will not utilize a tissue block if only 1 is available for each subject, to allow future clinical use such as re-evaluation or further studies.

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    Soo Min Lee, Nur S. Ismail, Dina M. Saleh
    Journal of Current Research in Oral Surgery.2025; 5(1): 70.     CrossRef
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Original Articles
The Smad4/PTEN Expression Pattern Predicts Clinical Outcomes in Colorectal Adenocarcinoma
Yumin Chung, Young Chan Wi, Yeseul Kim, Seong Sik Bang, Jung-Ho Yang, Kiseok Jang, Kyueng-Whan Min, Seung Sam Paik
J Pathol Transl Med. 2018;52(1):37-44.   Published online October 23, 2017
DOI: https://doi.org/10.4132/jptm.2017.10.20
  • 13,258 View
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AbstractAbstract PDFSupplementary Material
Background
Smad4 and PTEN are prognostic indicators for various tumor types. Smad4 regulates tumor suppression, whereas PTEN inhibits cell proliferation. We analyzed and compared the performance of Smad4 and PTEN for predicting the prognosis of patients with colorectal adenocarcinoma.
Methods
Combined expression patterns based on Smad4+/– and PTEN+/– status were evaluated by immunostaining using a tissue microarray of colorectal adenocarcinoma. The relationships between the protein expression and clinicopathological variables were analyzed.
Results
Smad4–/PTEN– status was most frequently observed in metastatic adenocarcinoma, followed by primary adenocarcinoma and tubular adenoma (p<.001). When Smad4–/PTEN– and Smad4+/PTEN+ groups were compared, Smad4–/PTEN– status was associated with high N stage (p=.018) and defective mismatch repair proteins (p=.006). Significant differences in diseasefree survival and overall survival were observed among the three groups (Smad4+/PTEN+, Smad4–/PTEN+ or Smad4+/PTEN–, and Smad4–/PTEN–) (all p<.05).
Conclusions
Concurrent loss of Smad4 and PTEN may lead to more aggressive disease and poor prognosis in patients with colorectal adenocarcinoma compared to the loss of Smad4 or PTEN alone.

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    Mona Hany Emile, Sameh Hany Emile, Amr Awad El-Karef, Mohamed Awad Ebrahim, Ibrahim Eldosoky Mohammed, Dina Abdallah Ibrahim
    Updates in Surgery.2024; 76(6): 2181.     CrossRef
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    Michela Roberto, Giulia Arrivi, Emanuela Pilozzi, Andrea Montori, Genoveffa Balducci, Paolo Mercantini, Andrea Laghi, Debora Ierinò, Martina Panebianco, Daniele Marinelli, Silverio Tomao, Paolo Marchetti, Federica Mazzuca
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  • Clinicopathological Characterization and Prognostic Implication of SMAD4 Expression in Colorectal Carcinoma
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  • Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
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  • Reply to: Dissecting the therapeutic implications of the complex SMAD4 regulatory network in metastatic colorectal cancer
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Implication of PHF2 Expression in Clear Cell Renal Cell Carcinoma
Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon
J Pathol Transl Med. 2017;51(4):359-364.   Published online June 13, 2017
DOI: https://doi.org/10.4132/jptm.2017.03.16
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AbstractAbstract PDF
Background
Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry.
Methods
We studied 254 CCRCCs and 56 non-neoplastic renal tissues from patients who underwent radical or partial nephrectomy between 2000 and 2003 at the Seoul National University Hospital. Tissue microarray blocks were prepared, and immunohistochemical staining for PHF2 was performed.
Results
Among 254 CCRCC cases, 150 cases (59.1%) showed high expression and 104 cases (40.1%) showed low expression. High expression of PHF2 was significantly correlated with a low Fuhrman nuclear grade (p < .001), smaller tumor size (p < .001), low overall stage (p = .003), longer cancer-specific survival (p = .002), and progression-free survival (p < .001) of the patients. However, it was not an independent prognostic factor in multivariate analysis adjusted for Fuhrman nuclear grade and overall stage.
Conclusions
Our study showed that low expression of PHF2 is associated with aggressiveness and poor prognosis of CCRCC.

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    Stella Pappa, Natalia Padilla, Simona Iacobucci, Marta Vicioso, Elena Álvarez de la Campa, Claudia Navarro, Elia Marcos, Xavier de la Cruz, Marian A. Martínez-Balbás
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  • Plant homeodomain finger protein 2 as a novel IKAROS target in acute lymphoblastic leukemia
    Zheng Ge, Yan Gu, Qi Han, Justin Sloane, Qinyu Ge, Goufeng Gao, Jinlong Ma, Huihui Song, Jiaojiao Hu, Baoan Chen, Sinisa Dovat, Chunhua Song
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Case Study
Perivascular Epithelioid Cell Tumor in the Stomach
Sun Ah Shin, Jiwoon Choi, Kyung Chul Moon, Woo Ho Kim
J Pathol Transl Med. 2017;51(4):428-432.   Published online April 4, 2017
DOI: https://doi.org/10.4132/jptm.2016.09.16
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AbstractAbstract PDF
Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST), and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

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  • A Perivascular Epithelioid Cell Tumor in the Ascending Colon: A Rare Case Involving a Patient With Tuberous Sclerosis
    Kai Seharada, Masato Kitazawa, Satoshi Nakamura, Yuta Yamamoto, Yuji Soejima
    Cureus.2025;[Epub]     CrossRef
  • Malignant Perivascular Epithelioid Cell Tumor of Ovary: A Rare Case Report
    Anuradha Sharma, Reetika Sharma, Jyoti Bala, Monika Sharma
    Journal of Mid-life Health.2025; 16(1): 107.     CrossRef
  • Unusual paediatric sigmoid perivascular epithelioid cell tumour with regional lymph node metastasis treated using gemcitabine and docetaxel: a case report and literature review
    Hsiu-Chung Cheng, Chia-Yu Kuo, Ching-Wen Huang, Hsiang-Hung Shih, Chih-Hung Lin, Jaw-Yuan Wang
    Journal of International Medical Research.2021;[Epub]     CrossRef
  • Gastric Perivascular Epithelioid Cell Tumor (PEComa)
    Jinghong Xu, Yu Yan, Xueping Xiang, Peter Jiang, Xiangrong Hu, Wenjun Yang
    American Journal of Clinical Pathology.2019; 152(2): 221.     CrossRef
  • Robotic wedge resection of a rare gastric perivascular epithelioid cell tumor: A case report
    Alessandra Marano, Francesca Maione, Yanghee Woo, Luca Pellegrino, Paolo Geretto, Diego Sasia, Mirella Fortunato, Giulio Fraternali Orcioni, Roberto Priotto, Renato Fasoli, Felice Borghi
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Original Articles
Detection of Human Papillomavirus in Korean Breast Cancer Patients by Real-Time Polymerase Chain Reaction and Meta-Analysis of Human Papillomavirus and Breast Cancer
Jinhyuk Choi, Chungyeul Kim, Hye Seung Lee, Yoo Jin Choi, Ha Yeon Kim, Jinhwan Lee, Hyeyoon Chang, Aeree Kim
J Pathol Transl Med. 2016;50(6):442-450.   Published online October 10, 2016
DOI: https://doi.org/10.4132/jptm.2016.07.08
  • 14,491 View
  • 226 Download
  • 16 Web of Science
  • 17 Crossref
AbstractAbstract PDF
Background
Human papillomavirus (HPV) is a well-established oncogenic virus of cervical, anogenital, and oropharyngeal cancer. Various subtypes of HPV have been detected in 0% to 60% of breast cancers. The roles of HPV in the carcinogenesis of breast cancer remain controversial. This study was performed to determine the prevalence of HPV-positive breast cancer in Korean patients and to evaluate the possibility of carcinogenic effect of HPV on breast.
Methods
Meta-analysis was performed in 22 case-control studies for HPV infection in breast cancer. A total of 123 breast cancers, nine intraductal papillomas and 13 nipple tissues of patients with proven cervical HPV infection were tested by real-time polymerase chain reaction to detect 28 subtypes of HPV. Breast cancers were composed of 106 formalin-fixed and paraffin embedded (FFPE) breast cancer samples and 17 touch imprint cytology samples of breast cancers.
Results
The overall odds ratio between breast cancer and HPV infection was 5.43 (95% confidence interval, 3.24 to 9.12) with I2 = 34.5% in meta-analysis of published studies with case-control setting and it was statistically significant. HPV was detected in 22 cases of breast cancers (17.9%) and two cases of intaductal papillomas (22.2%). However, these cases had weak positivity.
Conclusions
These results failed to serve as significant evidence to support the relationship between HPV and breast cancer. Further study with larger epidemiologic population is merited to determine the relationship between HPV and breast cancer.

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    Zhi-yong Liu, Ran Chen
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    G. M. Volgareva
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    Erika Maldonado-Rodríguez, Marisa Hernández-Barrales, Adrián Reyes-López, Susana Godina-González, Perla I. Gallegos-Flores, Edgar L. Esparza-Ibarra, Irma E. González-Curiel, Jesús Aguayo-Rojas, Adrián López-Saucedo, Gretel Mendoza-Almanza, Jorge L. Ayala-
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    Geilson Gomes de Oliveira, Ana Katherine Gonçalves, José Eleutério, Luiz Gonzaga Porto Pinheiro
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  • Oncogenic Viruses and Breast Cancer: Mouse Mammary Tumor Virus (MMTV), Bovine Leukemia Virus (BLV), Human Papilloma Virus (HPV), and Epstein–Barr Virus (EBV)
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    O.M. Gannon, A. Antonsson, I.C. Bennett, N.A. Saunders
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Clinical Significance of an HPV DNA Chip Test with Emphasis on HPV-16 and/or HPV-18 Detection in Korean Gynecological Patients
Min-Kyung Yeo, Ahwon Lee, Soo Young Hur, Jong Sup Park
J Pathol Transl Med. 2016;50(4):294-299.   Published online June 26, 2016
DOI: https://doi.org/10.4132/jptm.2016.05.09
  • 10,897 View
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  • 2 Crossref
AbstractAbstract PDF
Background
Human papillomavirus (HPV) is a major risk factor for cervical cancer.
Methods
We evaluated the clinical significance of the HPV DNA chip genotyping assay (MyHPV chip, Mygene Co.) compared with the Hybrid Capture 2 (HC2) chemiluminescent nucleic acid hybridization kit (Digene Corp.) in 867 patients.
Results
The concordance rate between the MyHPV chip and HC2 was 79.4% (kappa coefficient, κ = 0.55). The sensitivity and specificity of both HPV tests were very similar (approximately 85% and 50%, respectively). The addition of HPV result (either MyHPV chip or HC2) to cytology improved the sensitivity (95%, each) but reduced the specificity (approximately 30%, each) compared with the HPV test or cytology alone. Based on the MyHPV chip results, the odds ratio (OR) for ≥ high-grade squamous intraepithelial lesions (HSILs) was 9.9 in the HPV-16/18 (+) group and 3.7 in the non-16/18 high-risk (HR)-HPV (+) group. Based on the HC2 results, the OR for ≥ HSILs was 5.9 in the HR-HPV (+) group. When considering only patients with cytological diagnoses of “negative for intraepithelial lesion or malignancy” and “atypical squamous cell or atypical glandular cell,” based on the MyHPV chip results, the ORs for ≥ HSILs were 6.8 and 11.7, respectively, in the HPV-16/18 (+) group.
Conclusions
The sensitivity and specificity of the MyHPV chip test are similar to the HC2. Detecting HPV-16/18 with an HPV DNA chip test, which is commonly used in many Asian countries, is useful in assessing the risk of high-grade cervical lesions.

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  • Human papilloma virus identification in ocular surface squamous neoplasia by p16 immunohistochemistry and DNA chip test
    Tina Shrestha, Won Choi, Ga Eon Kim, Jee Myung Yang, Kyung Chul Yoon
    Medicine.2019; 98(2): e13944.     CrossRef
  • Comparison of the PANArray HPV Genotyping Chip Test with the Cobas 4800 HPV and Hybrid Capture 2 Tests for Detection of HPV in ASCUS Women
    Eun Young Ki, Yoon Kyung Lee, Ahwon Lee, Jong Sup Park
    Yonsei Medical Journal.2018; 59(5): 662.     CrossRef
Comparison of Analytical and Clinical Performance of HPV 9G DNA Chip, PANArray HPV Genotyping Chip, and Hybrid-Capture II Assay in Cervicovaginal Swabs
Ho Young Jung, Hye Seung Han, Hyo Bin Kim, Seo Young Oh, Sun-Joo Lee, Wook Youn Kim
J Pathol Transl Med. 2016;50(2):138-146.   Published online January 13, 2016
DOI: https://doi.org/10.4132/jptm.2015.10.21
  • 10,524 View
  • 68 Download
  • 4 Web of Science
  • 3 Crossref
AbstractAbstract PDF
Background
Human papillomavirus (HPV) infection can be detected by using several molecular methods, including Hybrid-Capture II (HC2) assay and variable HPV DNA chip tests, although each method has different sensitivities and specificities. Methods: We performed HPV 9G DNA Chip (9G) and PANArray HPV Genotyping Chip (PANArray) tests on 118 cervicovaginal swabs and compared the results with HC2, cytology, histology, and direct sequencing results. Results: The overall and high-risk HPV (HR-HPV) positivity rates were 62.7% and 44.9% using 9G, and 61.0% and 30.5% using PANArray, respectively. The positivity rates for HR-HPV with these two chips were significantly lower than 55.1% when HC2 was used. The sensitivity of overall HPV positivity in detecting histologically confirmed low-grade cervical squamous intraepithelial lesions or higher was 88.7% for all three tests. The specificity was 58.5% for 9G and 61.5% for PANArray, which was significantly lower than the 72.3% for HC2. With the HR-HPV+ genotype threshold, the sensitivity decreased to 75.5% for 9G and 52.8% for PANArray, which was significantly lower than the 88.7% for HC2. Comparison of the two chips showed concordant results in 55.1% of the samples, compatible results in 16.9%, and discordant results in 28.0%, exhibiting poor agreement in detecting  certain HPV genotypes. Compared with direct sequencing, 9G yielded no discordant results, whereas PANArray yielded 31 discordant results (26.7%). Conclusions: Compared with HC2, the HPV genotyping tests showed lower sensitivity in histologic correlation. When the two chips were compared, the 9G was more sensitive and accurate for detecting HR-HPV than the PANArray.

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  • Concordance of Anyplex™ II HPV HR assays with reference HPV assays in cervical cancer screening: Systematic review
    Habtamu Biazin
    Journal of Virological Methods.2022; 301: 114435.     CrossRef
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    Jiyoung Kim, Sun-Young Jun, Lee-So Maeng
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    Jiyoung Kim, Sun-Young Jun, Magdalena Grce
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Tongue Growth during Prenatal Development in Korean Fetuses and Embryos
Soo Jeong Hong, Bong Geun Cha, Yeon Sook Kim, Suk Keun Lee, Je Geun Chi
J Pathol Transl Med. 2015;49(6):497-510.   Published online October 16, 2015
DOI: https://doi.org/10.4132/jptm.2015.09.17
  • 15,579 View
  • 158 Download
  • 8 Web of Science
  • 15 Crossref
AbstractAbstract PDF
Background
Prenatal tongue development may affect oral-craniofacial structures, but this muscular organ has rarely been investigated. Methods: In order to document the physiology of prenatal tongue growth, we histologically examined the facial and cranial base structures of 56 embryos and 106 fetuses. Results: In Streeter’s stages 13–14 (fertilization age [FA], 28 to 32 days), the tongue protruded into the stomodeal cavity from the retrohyoid space to the cartilaginous mesenchyme of the primitive cranial base, and in Streeter’s stage 15 (FA, 33 to 36 days), the tongue rapidly swelled and compressed the cranial base to initiate spheno-occipital synchondrosis and continued to swell laterally to occupy most of the stomodeal cavity in Streeter’s stage 16–17 (FA, 37 to 43 days). In Streeter’s stage 18–20 (FA, 44 to 51 days), the tongue was vertically positioned and filled the posterior nasopharyngeal space. As the growth of the mandible and maxilla advanced, the tongue was pulled down and protruded anteriorly to form the linguomandibular complex. Angulation between the anterior cranial base (ACB) and the posterior cranial base (PCB) was formed by the emerging tongue at FA 4 weeks and became constant at approximately 124°–126° from FA 6 weeks until birth, which was consistent with angulations measured on adult cephalograms. Conclusions: The early clockwise growth of the ACB to the maxillary plane became harmonious with the counter-clockwise growth of the PCB to the tongue axis during the early prenatal period. These observations suggest that human embryonic tongue growth affects ACB and PCB angulation, stimulates maxillary growth, and induces mandibular movement to achieve the essential functions of oral and maxillofacial structures.

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Case Study
Human Herpesvirus 8-Negative and Epstein-Barr Virus-Positive Effusion-Based Lymphoma in a Patient with Human Immunodeficiency Virus
Jung-Woo Choi, Younghye Kim, Ju-Han Lee, Young-Sik Kim
J Pathol Transl Med. 2015;49(5):409-412.   Published online June 17, 2015
DOI: https://doi.org/10.4132/jptm.2015.06.03
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AbstractAbstract PDF
A 39-year-old man infected with human immunodeficiency virus (HIV) was admitted to our hospital because of sudden onset of chest pain. Chest radiography revealed pneumothorax of the right lung. Computed tomographic scans disclosed a 5.8-cm-sized emphysematous bulla in the right middle lobe of the lung. Histologically, the wedge-resected lung showed medium to large atypical cells within the bullous cavity of the Pneumocystis jirovecii pneumonia, without solid mass formation. These atypical cells were confirmed to be large B-cell lymphoma, Epstein-Barr virus–positive and human herpesvirus 8–negative. Therefore, this case was not diagnosed as primary effusion lymphoma, but effusion-based lymphoma arising in an emphysematous cavity of an HIV-infected patient. This type of effusion-based lymphoma has never been reported, and, although rare, it should be noted in order to clinically diagnose this lymphoma.

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  • Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics
    Savanah D. Gisriel, Ji Yuan, Ryan C. Braunberger, Danielle L.V. Maracaja, Xueyan Chen, Xiaojun Wu, Jenna McCracken, Mingyi Chen, Yi Xie, Laura E. Brown, Peng Li, Yi Zhou, Tarsheen Sethi, Austin McHenry, Ronald G. Hauser, Nathan Paulson, Haiming Tang, Eric
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Review
Current Concepts in Primary Effusion Lymphoma and Other Effusion-Based Lymphomas
Yoonjung Kim, Chan Jeong Park, Jin Roh, Jooryung Huh
Korean J Pathol. 2014;48(2):81-90.   Published online April 28, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.81
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AbstractAbstract PDF

Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8)-positive large B-cell neoplasm that presents as an effusion with no detectable tumor in individuals with human immunodeficiency virus infection or other immune deficiencies. PEL is an aggressive neoplasm with a poor prognosis. PEL cells show diverse morphologies, ranging from immunoblastic or plasmablastic to anaplastic. The immunophenotype of PEL is distinct, but its lineage can be misdiagnosed if not assessed thoroughly. PEL cells usually express CD45, lack B- and T-cell-associated antigens, and characteristically express lymphocyte activation antigens and plasma cell-associated antigens. Diagnosis of PEL often requires the demonstration of a B-cell genotype. HHV8 must be detected in cells to diagnose PEL. In most cases, PEL cells also harbor the Epstein-Barr virus (EBV) genome. Similar conditions associated with HHV8 but not effusion-based are called "extracavitary PELs." PELs should be differentiated from HHV8-negative, EBV-positive, body cavity-based lymphomas in patients with long-standing chronic inflammation; the latter can occur in tuberculous pleuritis, artificial pneumothorax, chronic liver disease and various other conditions. Despite their morphological similarity, these various lymphomas require different therapeutic strategies and have different prognostic implications. Correct diagnosis is essential to manage and predict the outcome of patients with PEL and related disorders.

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Original Articles
Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas
Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho
Korean J Pathol. 2014;48(1):43-49.   Published online February 25, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.43
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AbstractAbstract PDF
Background

Human papillomavirus (HPV) is an oncogenic virus in cervical cancer and most invasive carcinomas (ICs) are caused by HPV16 and 18. However, the roles and contributions of other uncommon and rare genotypes remain uncertain.

Methods

HPV genotypes were retrospectively assessed using an HPV DNA chip that can specify up to 32 HPV genotypes. We arbitrarily regarded genotypes accounting for less than 6% of the total as uncommon and rare genotypes.

Results

A total of 3,164 HPV-positive cases were enrolled. In groups 2A, 2B, 3, and unclassified HPV genotypes, 2.4% of cases with uncommon HPV genotypes (68, 26, 34, 53, 66, 69, 70, 73, 40, 42, 43, 44, 54, 55, 61, 62, 6, and 11) showed high grade squamous intraepithelial lesions and ICs. There were no HPV32- and 57-infected cases.

Conclusions

We found that the uncommon and rare HPV genotypes may provide incremental etiologic contributions in cervical carcinogenesis, especially HPV68, 70, and 53. Further studies on these uncommon and rare HPV genotypes will be of importance in establishing the significance of genotypes in different regions, especially in planning a strategy for further vaccine development as well as follow-up on the effectiveness of the currently used vaccines.

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Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors
Hyoun Wook Lee, Seung Yeon Ha, Mee Sook Roh
Korean J Pathol. 2014;48(1):17-23.   Published online February 25, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.17
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AbstractAbstract PDF
Background

Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.

Methods

Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).

Results

Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).

Conclusions

This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

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Immunohistochemical Classification of Primary and Secondary Glioblastomas
Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park
Korean J Pathol. 2013;47(6):541-548.   Published online December 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.541
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AbstractAbstract PDF
Background

Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.

Methods

We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.

Results

According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.

Conclusions

We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.

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MAD2 Expression in Ovarian Carcinoma: Different Expression Patterns and Levels among Various Types of Ovarian Carcinoma and Its Prognostic Significance in High-Grade Serous Carcinoma
Po Eun Park, Ji Yun Jeong, Sun Zoo Kim, Ji Young Park
Korean J Pathol. 2013;47(5):418-425.   Published online October 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.418
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AbstractAbstract PDF
Background

Mitotic arrest deficiency protein 2 (MAD2) is a key component of spindle assembly checkpoint function, which mediates cell apoptosis through microtubule kinetics. Aberrant expression of MAD2 is believed to be associated with the development of chromosome instability. MAD2 also has a signihicant role in cellular drug resistance to taxane chemotherapeutic agents.

Methods

Expression of MAD2 and p53 was investigated using immunohistochemistry in 85 cases of ovarian carcinomas. Clinicopathological data including progression-free survival were analyzed.

Results

A significant (p=.035) association was observed between the grade of serous carcinoma and the expression level of MAD2. While low-grade serous carcinoma showed a low-level expression of MAD2, high-grade serous carcinoma showed a high-level expression of MAD2. We also determined that low-level expression of MAD2 was associated with reduced progression-free survival (PFS) (p=.016) in high-grade serous carcinoma.

Conclusions

MAD2 expression in ovarian carcinoma is related to the grade of serous carcinoma and PFS of high-grade serous carcinoma. Expression level of MAD2 detected by immunohistochemistry may serve as an indicator in predicting the response of microtubule-interfering chemotherapeutic agents.

Citations

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Cytological Evaluation and REBA HPV-ID HPV Testing of Newly Developed Liquid-Based Cytology, EASYPREP: Comparison with SurePath
Youn Soo Lee, Gyungyub Gong, Jin Hee Sohn, Ki Sung Ryu, Jung Hun Lee, Shin Kwang Khang, Kyung-Ja Cho, Yong-Man Kim, Chang Suk Kang
Korean J Pathol. 2013;47(3):265-274.   Published online June 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.3.265
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AbstractAbstract PDF
Background

The objective of this study was to evaluate a newly-developed EASYPREP liquid-based cytology method in cervicovaginal specimens and compare it with SurePath.

Methods

Cervicovaginal specimens were prospectively collected from 1,000 patients with EASYPREP and SurePath. The specimens were first collected by brushing for SurePath and second for EASYPREP. The specimens of both methods were diagnosed according to the Bethesda System. Additionally, we performed to REBA HPV-ID genotyping and sequencing analysis for human papillomavirus (HPV) on 249 specimens.

Results

EASYPREP and SurePath showed even distribution of cells and were equal in cellularity and staining quality. The diagnostic agreement between the two methods was 96.5%. Based on the standard of SurePath, the sensitivity, specificity, positive predictive value, and negative predictive value of EASYPREP were 90.7%, 99.2%, 94.8%, and 98.5%, respectively. The positivity of REBA HPV-ID was 49.4% and 95.1% in normal and abnormal cytological samples, respectively. The result of REBA HPV-ID had high concordance with sequencing analysis.

Conclusions

EASYPREP provided comparable results to SurePath in the diagnosis and staining quality of cytology examinations and in HPV testing with REBA HPV-ID. EASYPREP could be another LBC method choice for the cervicovaginal specimens. Additionally, REBA HPV-ID may be a useful method for HPV genotyping.

Citations

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  • Virome capture sequencing for comprehensive HPV genotyping in cervical samples
    Thanayod Sasivimolrattana, Sasiprapa Liewchalermwong, Wasun Chantratita, Insee Sensorn, Arkom Chaiwongkot, Parvapan Bhattarakosol
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Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis
Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho
Korean J Pathol. 2013;47(2):148-157.   Published online April 24, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.148
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AbstractAbstract PDF
Background

Human papillomavirus (HPV)-related tonsillar squamous cell carcinoma (TSCC) has recently been characterized as a distinct subset with a favorable prognosis. The prevalence and clinicopathologic significance of HPV-related TSCC in Koreans are not well known.

Methods

HPV in situ hybridization (ISH) accompanied by p53, p16, pRb, and cyclin D1 immunohistochemical staining were performed on 89 resection cases of TSCC from 2000 through 2010.

Results

HPV was detected by ISH in 59 of 89 cases (66.3%). HPV-positive TSCCs were more common in younger ages (p=0.005), and tumor sizes were smaller in the HPV-positive compared to the HPV-negative group (p=0.040). Positive HPV staining was significantly correlated with p16 expression (p<0.001), pRb inactivation (p=0.003), and cyclin D1 down-regulation (p<0.001) but not with p53 expression (p=0.334). Seventeen cases that showed p16-immunopositivity with HPV-negativity by ISH were retested by HPV typing; HPV DNA was not detected in all cases. There was no significant difference between HPV-positive and HPV-negative patients either in the disease-specific survival (DSS, p=0.857) or overall survival (p=0.910). Furthermore, pRb-inactivated cases showed better DSS (p=0.023), and p53-positive cases showed worse DSS (p=0.001).

Conclusions

Although high HPV prevalence was noted, it was not correlated with histopathologic findings or survival benefit. In addition to p53 expression, pRb inactivation along with p16 overexpression and down-regulation of cyclin D1 are thought to be important pathogenetic steps for developing TSCCs.

Citations

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  • Assessment of the Mutation Profile of Tonsillar Squamous Cell Carcinomas Using Targeted Next-Generation Sequencing
    Ha Young Park, Joong Seob Lee, Jee Hye Wee, Jeong Wook Kang, Eun Soo Kim, Taeryool Koo, Hee Sung Hwang, Hyo Jung Kim, Ho Suk Kang, Hyun Lim, Nan Young Kim, Eun Sook Nam, Seong Jin Cho, Mi Jung Kwon
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Finding and Characterizing Mammary Analogue Secretory Carcinoma of the Salivary Gland
Min Jung Jung, Joon Seon Song, Sang Yoon Kim, Soon Yuhl Nam, Jong-Lyel Roh, Seung-Ho Choi, Sung-Bae Kim, Kyung-Ja Cho
Korean J Pathol. 2013;47(1):36-43.   Published online February 25, 2013
DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.36
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AbstractAbstract PDF
Background

A new tumor entity of the salivary glands, mammary analogue secretory carcinoma (MASC) with ETV6-NTRK3 translocation, has recently been proposed. MASC was originally diagnosed as adenocarcinoma, not otherwise specified (ANOS), or acinic cell carcinoma (AciCC) by the current World Health Organization classification. We aimed to identify MASC cases by molecular tests, and to characterize their clinical, histological, and immunohistochemical features.

Methods

Thirty cases of MASC candidates were selected after review of 196 salivary gland tumors, and subjected to break-apart ETV6 fluorescence in situ hybridization (FISH), and immunohistochemical study for S100 protein, gross cystic disease fluid protein 15, DOG1, estrogen receptor, and progesterone receptor.

Results

Valid FISH results were obtained in 23 cases, and 13 positive cases were retrieved. MASCs were histologically varied, and the most frequent features observed in 10 cases were low-grade papillary/cystic/glandular patterns, intraluminal secretory materials, ovoid/wrinkled nuclei, and relatively abundant granular eosinophilic cytoplasms, corresponding to papillary-cystic or follicular types of AciCC. All cases showed diffuse immunopositivity for S100 protein. Three cases developed recurrences, but all patients remained alive.

Conclusions

MASC could be a molecularly well-defined salivary gland neoplasm, encompassing some portions of AciCC and ANOS, but its histological spectrum and clinical implication require further investigation.

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Expression of SIRT1 and DBC1 in Gastric Adenocarcinoma
Youngran Kang, Woon Yong Jung, Hyunjoo Lee, Eunjung Lee, Aeree Kim, Baek-hui Kim
Korean J Pathol. 2012;46(6):523-531.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.523
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AbstractAbstract PDF
Background

Sirtuin 1 (SIRT1) and deleted in breast cancer 1 (DBC1) are known as tumor suppressor or promoter genes. This may be due to their diverse functions and interaction with other proteins. Gastric adenocarcinoma is one of the most common malignancies, but little is known about its carcinogenesis. Therefore, we investigated the association of immunohistochemical expression of SIRT1, DBC1, p53, and β-catenin and their variable clinicopathological characteristics.

Methods

We obtained samples from 452 patients who underwent gastrectomy. Tissue microarray blocks were constructed and immonohistochemical staining was performed.

Results

Expression of DBC1 and SIRT1 was associated with lower histologic grade, intestinal type of Lauren classification, and lower pT (p<0.001) and pN stage (DBC1, p=0.002; SIRT1, p<0.001). Association between absence of lymphatic invasion, and SIRT1 (p=0.001) and DBC1 (p=0.004) was observed. Cytoplasmic β-catenin expression was associated with lower histologic grade, pT, pN, tumor-node-metastasis (TNM) stage, DBC1 (p<0.001), and SIRT1 (p=0.001). Expression of SIRT1 and DBC1 was not associated with p53 (p=0.063 and p=0.060). DBC1 was an independent good prognostic factor in multivariate analysis (p=0.012).

Conclusions

SIRC1 and DBC1 can be considered to be good prognostic factors in gastric adenocarcinoma.

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Expression of c-Met Is Different along the Location and Associated with Lymph Node Metastasis of Head and Neck Carcinoma
Ji-Young Choe, Ji Yun Yun, Soo-Jeong Nam, Ji Eun Kim
Korean J Pathol. 2012;46(6):515-522.   Published online December 26, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.515
  • 9,420 View
  • 52 Download
  • 19 Crossref
AbstractAbstract PDF
Background

Activation of the c-Met pathway is involved in cancer progression and the prognosis. We aimed to identify any association of c-Met protein expression with a number of clinicopathologic variables including infection of human papillomavirus and Epstein-Barr virus (EBV) in head and neck carcinomas (HNCa).

Methods

Eighty-two cases were enrolled in this study. Expression of c-Met and p16 was investigated immunohistochemically. EBV was detected by in situ hybridization and amplification of the c-Met gene by fluorescence in situ hybridization.

Results

The c-Met protein was expressed in 41.5% (34/82), and gene amplification was found in 1.4% (1/71). High expression of c-Met was associated with the primary location of the tumor; the hypopharynx showed the highest expression, followed by the oral cavity, larynx, and nasal cavity. Squamous cell carcinoma expressed c-Met more frequently than undifferentiated carcinoma. Also, p16 immunoreactivity or EBV infection was associated with the tumor location and well-differentiated histologic type, but were not linked to c-Met expression. The patients with positive c-Met expression showed frequent lymph node metastasis.

Conclusions

Activation of the c-Met pathway might be involved in a subset of HNCa. Cases showing positive c-Met expression should be carefully monitored because of the high probability of lymph node metastasis.

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    Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
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Case Report
Primary Endometrial Squamous Cell Carcinoma: A Case Report and Review of Relevant Literature on Korean Women
Sung Jong Lee, Hyun Joo Choi
Korean J Pathol. 2012;46(4):395-398.   Published online August 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.395
  • 9,721 View
  • 85 Download
  • 15 Crossref
AbstractAbstract PDF

Primary endometrial squamous cell carcinoma (PESCC) is an extremely rare tumor with unclear pathogenesis. A 54-year-old postmenopausal woman presented with a 6-month history of vaginal bleeding. The patient was provisionally diagnosed with uterine submucosal leiomyoma. This was followed by total hysterectomy with a bilateral salpingo-oophorectomy under the laparoscopic guidance. Histopathologically, the tumor was PESCC which was accompanied by a lack of the tumor in the uterine cervix. The tumor showed positive immunoreactivity for p16INK4a. But there was no evidence of human papillomavirus (HPV) on in situ hybridization and HPV DNA chip analysis. We also present a review of the relevant literature on Korean women.

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Original Articles
Expression of Human Papillomavirus-Related Proteins and Its Clinical Implication in Tonsillar Squamous Cell Carcinoma
Joon Seon Song, Min-Sik Kim, Joon Wook Park, Youn Soo Lee, Chang Suk Kang
Korean J Pathol. 2012;46(2):177-186.   Published online April 25, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.177
  • 11,401 View
  • 42 Download
  • 9 Crossref
AbstractAbstract PDF
Background

Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC.

Methods

Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV.

Results

Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1).

Conclusions

Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.

Citations

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  • Positive Rate of Human Papillomavirus and Its Trend in Head and Neck Cancer in South Korea
    Hyun Woong Jun, Yong Bae Ji, Chang Myeon Song, Jae Kyung Myung, Hae Jin Park, Kyung Tae
    Frontiers in Surgery.2022;[Epub]     CrossRef
  • Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus–Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System
    Hyunchul Kim, Mi Jung Kwon, Bumjung Park, Hyo Geun Choi, Eun Sook Nam, Seong Jin Cho, Kyueng-Whan Min, Eun Soo Kim, Hee Sung Hwang, Mineui Hong, Taeryool Koo, Hyo Jung Kim
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    Krish Suresh, Parth V. Shah, Sydney Coates, Borislav A. Alexiev, Sandeep Samant
    American Journal of Otolaryngology.2021; 42(1): 102782.     CrossRef
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    Yuil Kim, Young-Hoon Joo, Min-Sik Kim, Youn Soo Lee
    Journal of Pathology and Translational Medicine.2020; 54(5): 411.     CrossRef
  • Human Papillomavirus Testing in Head and Neck Carcinomas: Guideline From the College of American Pathologists
    James S. Lewis, Beth Beadle, Justin A. Bishop, Rebecca D. Chernock, Carol Colasacco, Christina Lacchetti, Joel Todd Moncur, James W. Rocco, Mary R. Schwartz, Raja R. Seethala, Nicole E. Thomas, William H. Westra, William C. Faquin
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    Mi Jung Kwon, Dong Hoon Kim, Hye-Rim Park, Hyung Sik Shin, Ji Hyun Kwon, Dong Jin Lee, Jin Hwan Kim, Seong Jin Cho, Eun Sook Nam
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  • Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis
    Miji Lee, Sung Bae Kim, Sang-wook Lee, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho
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Detection of Survivin and COX-2 in Thyroid Carcinoma: Anaplastic Carcinoma Shows Overexpression of Nuclear Survivin and Low COX-2 Expression
Young A Kim, Meesoo Chang, Young Joo Park, Ji Eun Kim
Korean J Pathol. 2012;46(1):55-60.   Published online February 23, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.55
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AbstractAbstract PDF
Background

Overexpression of survivin, a member of the inhibitors of apoptosis protein, has been reported in various carcinomas, and its interaction with cyclooxygenase 2 (COX-2) results in accelerated tumor progression. The purpose of this study is to investigate the immunohistochemical expression of survivin and COX-2 in benign and malignant thyroid tissues and to define its association with pathologic and clinical features.

Methods

We examined expression of survivin and COX-2 by immunohistochemistry in 334 benign and malignant thyroid tissues and evaluated their clinical significance.

Results

Expression of survivin showed an increase along the spectrum of thyroid carcinoma progression; rarely positive in adenomatous goiter, moderately positive in papillary carcinoma, and strongly positive in anaplastic carcinoma (AC). Papillary microcarcinoma revealed the highest COX-2 positivity and AC demonstrated the lowest positivity among thyroid cancers. Node negative carcinomas showed higher COX-2 expression than node positive tumors. Survivin expression did not correlate with COX-2.

Conclusions

Our findings suggest that survivin overexpression may be related to the pathogenesis of AC and can be a predictor of disease progression. COX-2 may be involved in the early phase of thyroid carcinoma.

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    Adesh D. Vaidya, Alexander J. Fezovich, Sally P. Wheatley
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    Xiaoyan Fu, Huayong Zhang, Zhipeng Chen, Zhongyuan Yang, Dingbo Shi, Tianrun Liu, Weichao Chen, Fan Yao, Xuan Su, Wuguo Deng, Miao Chen, Ankui Yang
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    Min Hye Jang, Kyeong Cheon Jung, Hye Sook Min
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    Sonja Selemetjev, Tijana Isic Dencic, Ilona Marecko, Jelena Jankovic, Ivan Paunovic, Svetlana Savin, Dubravka Cvejic
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Inhibitors of Apoptosis Proteins Expression and Their Prognostic Significance in Colorectal Carcinoma.
Kyung Hwa Lee, Soong Lee, Hyeon Min Lee, Seung Chul Back, Sung Bum Cho, Jae Hyuk Lee
Korean J Pathol. 2011;45(4):397-405.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.397
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AbstractAbstract PDF
BACKGROUND
The expression of the inhibitor of apoptosis proteins (IAPs) family has not been fully investigated in colorectal carcinomas. This study investigated IAP expression in colorectal carcinomas and assessed their prognostic significance.
METHODS
Livin, XIAP, and SMAC/DIABLO expression was assessed by immunohistochemistry in 159 colorectal carcinomas. Correlations between protein expression and clinicopathological features were evaluated. The survival data analysis was estimated according to the Kaplan-Meier method.
RESULTS
Increased expression of IAPs in cancer tissues compared to surrounding nonneoplastic counterparts was observed in 67 cases (42.1%) for Livin, 50 cases (31.4%) for XIAP, and 68 cases (42.8%) for SMAC. A significant correlation was found between Livin expression and tumor differentiation, and SMAC expression and tumor location. The recurrence-free and overall survival of patients with low Livin expression were inferior to those of patients with high Livin expression (p=0.054 and 0.095, respectively). High XIAP expression was significantly associated with shorter progression-free survival (p= 0.041).
CONCLUSIONS
Our study demonstrated that altered expression of IAP family members, including Livin, XIAP, and SMAC, is frequent in colorectal carcinoma. This result suggests that high Livin expression and low XIAP expression may be a favorable prognostic implication related to patient survival.

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  • A Review of the Current Impact of Inhibitors of Apoptosis Proteins and Their Repression in Cancer
    Pierina Cetraro, Julio Plaza-Diaz, Alex MacKenzie, Francisco Abadía-Molina
    Cancers.2022; 14(7): 1671.     CrossRef
Human Papillomavirus Prevalence in Gangwon Province Using Reverse Blot Hybridization Assay.
Dongsup Lee, Sunghyun Kim, Sangjung Park, Hyunwoo Jin, Tae Ue Kim, Kwang Hwa Park, Hyeyoung Lee
Korean J Pathol. 2011;45(4):348-353.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.348
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AbstractAbstract PDF
BACKGROUND
Human papillomavirus (HPV) plays an important role in the development of cervical carcinoma. Although there is a general agreement that high levels of HPV are related to cervical cancer, the prevalence and distribution of HPV genotypes seems to vary by geographical region. This study was designed to investigate the prevalence of HPV genotypes in Gangwon Province, Korea.
METHODS
In total, 342 samples were examined by Pap smear and HPV-ID(R) reverse blot hybridization assay (REBA) (M&D, Wonju, Korea).
RESULTS
Overall HPV positivity was 80.9% and 64.4% in women with abnormal and normal cytology by REBA, respectively. The five most common HPV types were: HPV 16, 53, 58, 56, and 33 in samples with abnormal cytology, and HPV 16, 53, 58, 70, and 18 in samples with normal cytology.
CONCLUSIONS
The REBA can provide useful data regarding prevalence of HPV genotypes. Gangwon Province showed high prevalence of HPV infection in women. The most common HPV type in Gangwon Province was HPV16, and HPV 53, 58, 56, 70 were frequently present.

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  • Human Papillomavirus (HPV69/HPV73) Coinfection associated with Simultaneous Squamous Cell Carcinoma of the Anus and Presumed Lung Metastasis
    Stephanie Shea, Marina Muñoz, Stephen C. Ward, Mary B. Beasley, Melissa R Gitman, Michael D Nowak, Jane Houldsworth, Emilia Mia Sordillo, Juan David Ramirez, Alberto E. Paniz Mondolfi
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    Geehyuk Kim, Sungyoung Park, Hye-young Wang, Sunghyun Kim, Sangjung Park, Kwangmin Yu, Boohyung Lee, Seung-Ju Ahn, Eun-Joong Kim, Dongsup Lee
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    Geehyuk Kim, Sunghyun Kim, Sunyoung Park, Sangjung Park, Han Lin, Yubo Ren, Li Yingxue, In Soo Lee, Jae Dal Lee, Dongsup Lee
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    In Hee Lee, Yoo Hyun Kim
    Korean Journal of Clinical Laboratory Science.2015; 47(4): 306.     CrossRef
  • Diagnostic Performance of HPV E6/E7 mRNA and HPV DNA Assays for the Detection and Screening of Oncogenic Human Papillomavirus Infection among Woman with Cervical Lesions in China
    Hye-young Wang, Dongsup Lee, Sunyoung Park, Geehyuk Kim, Sunghyun Kim, Lin Han, Ren Yubo, Yingxue Li, Kwang Hwa Park, Hyeyoung Lee
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  • Uncommon and Rare Human Papillomavirus Genotypes Relating to Cervical Carcinomas
    Na Rae Kim, Myunghee Kang, Soon Pyo Lee, Hyunchul Kim, Jungsuk An, Dong Hae Chung, Seung Yeon Ha, Hyun Yee Cho
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Expression of Multidrug Resistance Protein 1 in Human Hepatocellular Carcinoma.
Yun Kyung Kang
Korean J Pathol. 2011;45(3):281-289.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.281
  • 4,565 View
  • 28 Download
  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Multidrug resistance protein 1 (MDR1) encoded by ATP-binding cassette, sub-family B (Mdr/Tap), member 1 (ABCB1) mediates cross-resistance to antineoplastic drugs, and its expression is related to tumor aggressiveness.
METHODS
MDR1 expression was investigated in 100 hepatocellular carcinomas (HCCs) by immunohistochemical staining. The epigenetic mechanisms underlying ABCB1 transcriptional regulation were investigated in cell lines.
RESULTS
MDR1 was normally localized in the bile canalicular surface of the hepatocytes. Among 100 HCCs, 45 showed canalicular/luminal (CL) staining similar to the normal pattern, another 45 displayed membranous/cytoplasmic (MC) overexpression, and the remaining 10 revealed loss of expression. MC pattern or null staining of HCCs correlated with a higher histological grade and had a poorer prognosis than HCCs with a CL pattern (p<0.05). They also tended to have a poor prognosis by multivariate survival analysis. The ABCB1 promoter was hypomethylated regardless of MDR1 expression or ABCB1 mRNA levels in 10 HCC cell lines. Histone deacetylase inhibitor treatment induced ABCB1 upregulation in 4 cell lines with low or moderate ABCB1 levels.
CONCLUSIONS
Our findings suggest that either an increase or a loss of MDR1 expression may contribute to the poor outcome of HCCs; histone deacetylation may be one of the epigenetic mechanisms directing the ABCB1 expression in HCCs.

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  • Preferential expression of prostate specific membrane in CD34 labeled Neo-vasculature of Hepatocellular carcinoma: Prognostic and therapeutic potentials
    Safaa MM Abd El Khalek, Mona QR Mohammed, Amira M Al Balakosy
    Egyptian Journal of Pathology.2023; 43(1): 66.     CrossRef
Copy Number Alterations of BCAS1 in Squamous Cell Carcinomas.
Yu Im Kim, Ahwon Lee, Jennifer Kim, Bum Hee Lee, Sung Hak Lee, Suk Woo Nam, Sug Hyung Lee, Won Sang Park, Nam Jin Yoo, Jung Young Lee, Sang Ho Kim, Su Young Kim
Korean J Pathol. 2011;45(3):271-275.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.271
  • 4,642 View
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AbstractAbstract PDF
BACKGROUND
Breast carcinoma amplified sequence 1 (BCAS1), located in 20q13, is amplified and overexpressed in breast cancers. Even though BCAS1 is expected to be an oncogene candidate, its contribution to tumorigenesis and copy number status in other malignancies is not reported. To elucidate the role of BCAS1 in squamous cell carcinomas, we investigated the copy number status and expression level of BCAS1 in several squamous cell carcinoma cell lines, normal keratinocytes and primary tumors.
METHODS
We quantitated BCAS1 gene by real-time polymerase chain reaction (PCR). Expression level of BCAS1 was measured by real-time reverse transcription-PCR and immunoblot.
RESULTS
Seven (88%) of 8 squamous cell carcinoma cell lines showed copy number gain of BCAS1 with various degrees. BCAS1 gene in primary tumors (73%) also showed copy number gain. However, expression level did not show a linear correlation with copy number changes.
CONCLUSIONS
We identified copy number gain of BCAS1 in squamous cell carcinomas. Due to lack of linear correlation between copy numbers of BCAS1 and its expression level, we could not confirm that the overexpression of BCAS1 is a common finding in squamous cell carcinoma cell lines. However, this study shows that the copy number gain of BCAS1 is a common finding in squamous cell carcinomas.

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  • Electrochemical Approaches for Preparation of Tailor-Made Amino Acids
    Nana Wang, Jingcheng Xu, Haibo Mei, Hiroki Moriwaki, Kunisuke Izawa, Vadim A. Soloshonok, Jianlin Han
    Chinese Journal of Organic Chemistry.2021; 41(8): 3034.     CrossRef
Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer.
Hanna Kang, Harin Cheong, Min Sun Cho, Heasoo Koo, Woon Sup Han, Kyung Eun Lee, Byung In Moon, Sun Hee Sung
Korean J Pathol. 2011;45(1):53-61.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.53
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AbstractAbstract PDF
BACKGROUND
Triple negative breast cancer (TNBC) is defined as a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 in breast cancer. Many TNBCs show a profound infiltration of tumor infiltrating lymphocytes (TILs). It is still uncertain whether these TILs are protumoral or antitumoral. Regulatory T cells (Tregs) play a role in inducing immune tolerance to antigens, and they may be selectively recruited by cancer cells. This study was conducted to evaluate the significance of TILs with an emphasis on forkhead box p3 (Foxp3), which is a marker for CD25+CD4+ Treg in TNBC.
METHODS
We investigated the Foxp3, CD8 and CD4 expressions in 100 cases of TNBC by immunohistochemistry and using a tissue microarray. The Foxp3 expression was divided as the high and low infiltration groups (cut-off value=20).
RESULTS
The high infiltration group was correlated with higher histologic and nuclear grades. However, Foxp3+ Tregs were decreased in the T3 and T4 TNBCs as compared to that of the T1 and T2 TNBCs. No significant differences were found for the nodal status, lymphovascular invasion, stage, recurrence and overall survival.
CONCLUSIONS
High Foxp3+ Treg infiltration in TNBC is correlated with the nuclear and histologic grades, but there was no relation to recurrence and overall survival.

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  • Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer
    In Hye Song, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, In Ah Park, Young-Ae Kim, Suk Young Park, Jin Roh, Gyungyub Gong, Hee Jin Lee
    Cancer Research and Treatment.2017; 49(2): 399.     CrossRef
  • Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer
    Sewha Kim, Anbok Lee, Woosung Lim, Sanghui Park, Min Sun Cho, Heasoo Koo, Byung-In Moon, Sun Hee Sung
    Journal of Breast Cancer.2014; 17(1): 8.     CrossRef
ERCC1 Predicts a Poorer Platinum-based Chemotherapy Outcome but a Better Outcome for Uracil-Tegafur in the Resected Stage I-II NSCLC.
Han Suk Ryu, Xianhua Xu, Hyojin Kim, Jong Suk Lee, Sanghoon Jheon, Jin Haeng Chung
Korean J Pathol. 2011;45(1):45-52.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.45
  • 3,357 View
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AbstractAbstract PDF
BACKGROUND
The role of excision repair cross-complementation group 1 (ERCC1) has been controversial in non-small cell lung cancer (NSCLC) patients who received adjuvant chemotherapy with a platinum agent. We investigated ERCC1 expression in stage I-II NSCLC to clarify its significance for adjuvant chemotherapy.
METHODS
The ERCC1 expression profile was evaluated by immunohistochemistry and compared according to adjuvant chemotherapeutic agents in 146 patients who underwent surgical resection for stage I-II NSCLC. The patients were divided into 3 groups; adjuvant chemotherapy with a platinum based agent (18.5%, 27/146); adjuvant chemotherapy with uracil-tegafur (UFT) (40.4%, 59/146); surgery-alone (41.1%, 60/146).
RESULTS
Nuclear ERCC1 expression was detected in 71.9% (105/146) of NSCLC and was significantly associated with a shortened survival period in the group 1 patients who received the platinum based regimen after surgery. The group 2 patients who received UFT showed the longest survival period, followed by the surgery-alone group (overall survival, p=0.049; disease-free survival [DFS], p<0.001).
CONCLUSIONS
These results suggest that stage I-II NSCLC patients with ERCC1 expression experience a shorter DFS period with adjuvant chemotherapy with a platinum based regimen and may benefit from adjuvant chemotherapy with UFT, instead of platinum after surgery.
A Consideration of MGMT Gene Promotor Methylation Analysis for Glioblastoma Using Methylation-Specific Polymerase Chain Reaction and Pyrosequencing.
Sang Hwa Lee, Tae Sook Hwang, Young Cho Koh, Wook Youn Kim, Hye Seung Han, Wan Seop Kim, Young Sin Ko, So Dug Lim
Korean J Pathol. 2011;45(1):21-29.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.21
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AbstractAbstract PDF
BACKGROUND
O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is currently the most promising predictive marker for the outcome and benefit from temozolomide treatment in patients with glioblastoma, but there is no consensus on the analysis method for assessing the methylation status in the molecular diagnostic field. The objective of this study was to evaluate methylation-specific polymerase chain reaction (MSP) and pyrosequencing methods for assessing MGMT gene promotor methylation of glioblastoma as well as assessing the MGMT protein expression by immunohistochemistry.
METHODS
Twenty-seven cases of glioblastoma from the archives at the Department of Pathology Konkuk University Hospital were selected. MGMT promoter methylation was evaluated by MSP and the pyrosequencing methods. The MGMT expression was also measured at the protein level by immunohistochemistry.
RESULTS
Overall, MGMT hypermethylation was observed in 44.4% (12/27 cases) of the case of glioblastoma using either MSP or pyrosequencing. The concordant rate was 70.3% (19/27 cases) between MSP and pyrosequencing for MGMT methylation. There was no correlation between MGMT methylation and the protein expression. No significant differences in progression free survival and overall survival were seen between the methylated group and the unmethylated group by using either MSP or pyrosequencing. The status of the MGMT protein expression was correlated with progression free survival (p=0.026).
CONCLUSIONS
In this study the concordance rate between MSP and the pyrosequencing methods for assessing MGMT gene promotor methylation was relatively low for the cases of glioblastoma. This suggests that more reliable techniques for routine MGMT methylation study of glioblastoma remain to be developed because of quality control and assurance issues.

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  • Prognostic Role of Methylation Status of theMGMTPromoter Determined Quantitatively by Pyrosequencing in Glioblastoma Patients
    Dae Cheol Kim, Ki Uk Kim, Young Zoon Kim
    Journal of Korean Neurosurgical Society.2016; 59(1): 26.     CrossRef
  • Distinct genetic alterations in pediatric glioblastomas
    Sun-ju Byeon, Jae Kyung Myung, Se Hoon Kim, Seung-Ki Kim, Ji Hoon Phi, Sung-Hye Park
    Child's Nervous System.2012; 28(7): 1025.     CrossRef
  • MGMTGene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour
    Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim
    The Korean Journal of Pathology.2011; 45(5): 455.     CrossRef
Prognostic Implications of the Expression of CXCL16 in Breast Carcinoma.
Dong Youl Choi, Ran Hong, Sung Churl Lim, Keun Hong Kee, Chae Hong Suh, Mija Lee
Korean J Pathol. 2011;45(1):15-20.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.15
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AbstractAbstract PDF
BACKGROUND
Of the many prognostic factors for breast cancer, the relationship between an infiltration of inflammatory cells and the prognosis is debatable. Of the chemokines affecting cancer's inflammatory reactions, chemokine (C-X-C motif) ligand 16 (CXCL16) has attracted attention for its prognostic value in many cancers, including colorectal cancer and renal cell carcinoma. But the situation for breast carcinoma is unknown. The aim of this study was to examine the relationship between the prognostic factors and the CXCL16 expression in patients with breast carcinoma.
METHODS
The patients (n=106) diagnosed with invasive ductal cancer of the breast were enrolled. We reviewed the clinicopathological factors of these patients, hematoxylin and eosin stains were prepared and estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2/neu) and CXCL16 immunostaining was performed.
RESULTS
The ER expression was significantly correlated with age and inflammation. A CXCL16 expression was noted in 81.1% of the cases. No association was evident between a CXCL16 expression and any other parameter, including the survival rate. Multivariate analysis did not implicate ER, HER2/neu or CXCL16 as an independent prognostic factor, but the tumor size was independent predictive factor for the patient outcome.
CONCLUSIONS
An inflammatory reaction mediated by CXCL16 is not associated with the prognosis of breast cancer or any clinicopathological factors.

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  • The Emerging Role of CXC Chemokines And Their Receptors in Cancer
    Victoria Vinader, Kamyar Afarinkia
    Future Medicinal Chemistry.2012; 4(7): 853.     CrossRef
IMP3 Expression of the Cholangiocarcinoma in Cytology Specimen and Its Diagnostic Value.
Jung Wook Yang, Jong Sil Lee, Dong Chul Kim, Dae Hyun Song, Gyung Hyuck Ko, Jeong Hee Lee
Korean J Pathol. 2010;44(6):642-650.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.642
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AbstractAbstract PDF
BACKGROUND
Pathologists occasionally have difficulty in distinguishing cholangiocarcinoma from benign reactive cells on the biliary cytology. We estimated the diagnostic value of insulinlike growth factor II mRNA binding protein 3 (IMP3) on biliary cytology specimens.
METHODS
We selected 40 patients who had undergone a biliary cytology examination and whose diagnoses were confirmed by biopsy. The IMP3 expression was evaluated by immunohistochemical staining in both the tissue and the cytology specimens. Their histologic diagnoses were cholangiocarcinoma (n = 34), high grade dysplasia (n = 2), low grade dysplasia (n = 1) and non-biliary tumor or no tumor (n = 3).
RESULTS
On the histology, all the cases of cholangiocarcinoma or high grade dysplasia were positive for IMP3 (36/36). The low grade dysplasia or the normal bile ducts in the other 4 cases were negative for IMP3 (0/4). Of the 36 cases diagnosed as cholangiocarcinoma or high grade dysplasia histologically, 29 cases were positive for IMP3 on the cytology (29/36; sensitivity, 80.6%). Of the 4 cases without cholangiocarcinoma or high grade dysplasia, 1 case was weakly positive for IMP3 on the cytology. The histologic diagnosis of this case was hepatocellular carcinoma. Except for this hepatocellular carcinoma case, the specificity of IMP3 on the cytology was 100%.
CONCLUSIONS
IMP3 is a useful diagnostic marker for cholangiocarcinoma on cytology.

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  • Insulin-like Growth Factor II mRNA-Binding Protein 3 Expression in Benign and Premalignant Lesions and Carcinomas of the Stomach
    Dae Hyun Song, Jung Wook Yang, Dong Chul Kim, Jong Sil Lee, Jeong Hee Lee, Sang Ho Jeong, Gyung Hyuck Ko
    The Korean Journal of Pathology.2011; 45(4): 379.     CrossRef
p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors.
Seok Ju Park, Woo Jung Sung, Mi Jin Kim
Korean J Pathol. 2010;44(6):597-604.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.6.597
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AbstractAbstract PDF
BACKGROUND
At present, adequate prognostic markers for prostate cancer progression are still lacking, in spite of intensive investigation. Accordingly, our study examined the relationship between expression of candidate biomarkers and metastasis in prostate cancer patients. Correlation of molecular markers with prostate-specific antigen (PSA) level, Gleason sum score and tumor stage were also evaluated.
METHODS
A total of 105 prostate tumor specimens and specimens from 19 cases of nodular hyperplasia were obtained through Yeungnam University Hospital from 2007 to 2008. Immunohistochemical analyses for p16INK4a, phosphatase and tensin homolog (PTEN), E-cadherin, Ki-67 and Bcl-2 were performed.
RESULTS
Overexpression of Bcl-2 was significantly related to bone (p = 0.006) and nodal metastases (p = 0.017). Other biomarkers were not related to metastatic potential. There were statistically significant relationships between increased PSA level and loss of expression of PTEN (p = 0.019) and E-cadherin (p = 0.001). High Ki-67 index was significantly correlated with nodal metastasis (p = 0.029) as well as with loss of p16INK4a expression (p = 0.002) and high Gleason score (p = 0.011).
CONCLUSIONS
High Gleason score, Bcl-2 overexpression and increased Ki-67 labeling have significant predictive value in assessing the potential for prostate cancer metastasis. In addition, a high Ki-67 index is related to high Gleason score and loss of p16INK4a expression.

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  • Over-expression of β-catenin is associated with high grade of prostatic cancer in Libyan patients
    W. Said, F. Emaetig, K. El Gehani, T. Eldarat, A. Buhmeida, N. Enattah, A. Elzagheid, O. Al-Fituri
    African Journal of Urology.2017; 23(2): 133.     CrossRef
  • Bcl2 en cáncer avanzado de próstata y asociación con resistencia a la castración
    R.F. Velázquez-Macías, F.E. De La Torre-Rendón, G. Ramos-Rodríguez, C.A. Calzada-Mendoza, R.M. Coral-Vázquez
    Revista Mexicana de Urología.2016; 76(5): 288.     CrossRef
  • Hedgehog signaling protein expression and its association with prognostic parameters in prostate cancer: A retrospective study from the view point of new 2010 anatomic stage/prognostic groups
    Tae‐Jung Kim, Ji Youl Lee, Tae‐Kon Hwang, Chang Suk Kang, Yeong‐Jin Choi
    Journal of Surgical Oncology.2011; 104(5): 472.     CrossRef
HER2 Status in Gastric Adenocarcinomas Assessed by Immunohistochemistry, Automated Silver-Enhanced In Situ Hybridization and Fluorescence In Situ Hybridization.
Aeri Kim, Jung Min Bae, Se Won Kim, Mi Jin Gu, Young Kyung Bae
Korean J Pathol. 2010;44(5):493-501.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.493
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AbstractAbstract PDF
BACKGROUND
Recently, many studies have focused on human epidermal growth factor receptor 2 (HER2) status in gastric cancer due to HER2-targeted therapy using trastuzumab. We investigated HER2 overexpression and amplification and their concordance rate in Korean gastric adenocarcinomas.
METHODS
Tissue microarrays were constructed with 232 gastric adenocarcinoma samples. We performed immunohistochemistry (IHC), silver-enhanced in situ hybridization (SISH) and fluorescence in situ hybridization (FISH) for HER2.
RESULTS
IHC was negative in 94.8% (218/232), equivocal in 1.7% (4/232) and positive in 3.5% (8/232) of cases. HER2 protein expression was heterogeneous in 75% (9/12) of IHC 2+/3+ cancers. Gene amplification was observed in 6.5% (15/230) by SISH and the same 15 cases were also FISH-positive. We observed HER2 amplification in 1.4%, 27.3%, 25%, and 100% of IHC 0, 1+, 2+, and 3+ gastric adenocarcinomas, respectively. The concordance rate between IHC and SISH results was 95.7%.
CONCLUSIONS
HER2 overexpression and amplification were less frequent in gastric adenocarcinomas than breast carcinomas. Compared to breast carcinoma, (1) there may be IHC-negative but gene amplification-positive cases for HER2 and (2) frequent intratumoral heterogeneity of IHC for HER2 in gastric adenocarcinomas.

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  • Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer
    Kyung Won Seo, Taeyong Jeon, Sewon Kim, Sung Soo Kim, Kwanghee Kim, Byoung-Jo Suh, Sunhwi Hwang, SeongHee Choi, Seungwan Ryu, Jae Seok Min, Young-Joon Lee, Ye Seob Jee, Hyeondong Chae, Doo Hyun Yang, Sang Ho Lee
    Journal of Gastric Cancer.2017; 17(1): 52.     CrossRef
  • Synopsis on Clinical Practice Guideline of Gastric Cancer in Korea: An Evidence-Based Approach
    Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S
    The Korean Journal of Gastroenterology.2014; 63(2): 66.     CrossRef
  • Clinical Practice Guidelines for Gastric Cancer in Korea: An Evidence-Based Approach
    Jun Haeng Lee, Jae G. Kim, Hye-Kyung Jung, Jung Hoon Kim, Woo Kyoung Jeong, Tae Joo Jeon, Joon Mee Kim, Young Il Kim, Keun Won Ryu, Seong-Ho Kong, Hyoung-Il Kim, Hwoon-Yong Jung, Yong Sik Kim, Dae Young Zang, Jae Yong Cho, Joon Oh Park, Do Hoon Lim, Eun S
    Journal of Gastric Cancer.2014; 14(2): 87.     CrossRef
Clinicopathological Significance of S100A4 Expression in Non-small Cell Lung Carcinomas.
Eun Ah Jung, Hyun Deuk Cho, Ji Hye Lee, Mee Hye Oh
Korean J Pathol. 2010;44(5):477-482.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.477
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AbstractAbstract PDF
BACKGROUND
S100A4 has been implicated in invasion and metastasis of various malignant tumors. The aim of this study was to investigate whether or not S100A4 plays an important role in non-small cell lung carcinomas (NSCLCs).
METHODS
Sixty-seven patients with NSCLC including 37 with squamous cell carcinomas (SCCs) and 30 with adenocarcinomas (ADs) who had undergone surgical resection were analyzed. S100A4 expression was analyzed by immunohistochemistry using tissue microarray blocks.
RESULTS
S100A4 expression was positive in 56 (83.6%) of 67 NSCLC cases. ADs were more frequently S100A4 positive than SCCs (p = 0.017). However, no significant correlation was observed between S100A4 expression and age, gender, pT, pN or tumor, node and metastasis (TNM) stage. Two distant metastatic cases revealed an S100A4 positive reaction. Kaplan-Meier survival curves with the log-rank test showed no correlation with 3-year survival (p = 0.782) or 5-year survival (p = 0.227) in either group of patients according to S100A4 expression.
CONCLUSIONS
S100A4 expression was not correlated with age, gender, pT, pN or TNM stage or survival in patients with NSCLCs. Therefore, S100A4 expression may not be useful as a prognostic marker for NSCLCs. However, S100A4 expression showed a higher positivity in ADs than in SCCs.

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  • Clinicopathological and prognostic value of S100A4 expression in non-small cell lung cancer: a meta-analysis
    Jing Zhang, Yanhui Gu, Xiaoli Liu, Ximin Rao, Guichuan Huang, Yao Ouyang
    Bioscience Reports.2020;[Epub]     CrossRef
  • S100A4 promotes endometrial cancer progress through epithelial-mesenchymal transition regulation
    TENG HUA, SHUANGGE LIU, XIAOYAN XIN, LIQIONG CAI, RUI SHI, SHUQI CHI, DILU FENG, HONGBO WANG
    Oncology Reports.2016; 35(6): 3419.     CrossRef
  • Prognostic value of cytoplasmic expression of S100A4 protein in endometrial carcinoma
    HYE IN CHONG, JEONG HEE LEE, MAN SOO YOON, DONG SOO SUH, KYUNGBIN KIM, JEE YEON KIM, KYUNG UN CHOI
    Oncology Reports.2014; 31(6): 2701.     CrossRef
  • Clinical significance of E-cadherin, β-catenin, vimentin and S100A4 expression in completely resected squamous cell lung carcinoma
    Hua Zhang, Jun Liu, Dongsheng Yue, Liuwei Gao, Daowei Wang, Hongdian Zhang, Changli Wang
    Journal of Clinical Pathology.2013; 66(11): 937.     CrossRef
  • Expression of S100A4, ephrin-A1 and osteopontin in non-small cell lung cancer
    Ane Kongsgaard, Marius Lund-Iversen, Gisle Berge, Odd Terje Brustugun, Steinar K Solberg, Gunhild M Mælandsmo, Kjetil Boye
    BMC Cancer.2012;[Epub]     CrossRef
  • Clinicopathologic Implication of Ezrin Expression in Non-small Cell Lung Cancer
    Ho Won Lee, Eui Han Kim, Mee-Hye Oh
    Korean Journal of Pathology.2012; 46(5): 470.     CrossRef
Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma.
Ji Min Jeon, Hye Won Lee, Ji Young Park, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Mi Sun Choe, Yu Na Kang, Sang Pyo Kim, Sang Sook Lee, Won Il Choi, Kun Young Kwon
Korean J Pathol. 2010;44(4):397-403.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.397
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AbstractAbstract PDF
BACKGROUND
Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance.
METHODS
We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray.
RESULTS
We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128).
CONCLUSIONS
MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.

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  • Inhibition of MUC1-C Increases ROS and Cell Death in Mouse Embryonic Stem Cells
    Jeong-A Park, Sangkyu Park, Jun-Kyu Choi, Myung-Kwan Han, Younghee Lee
    International Journal of Stem Cells.2020;[Epub]     CrossRef
  • Assessing the prognostic significance of MUC4β in mucoepidermoid carcinoma of the salivary glands: An immunohistochemical study
    Poonam R. Sawant, Anita Spadigam, Anita Dhupar, Shaheen Syed, Karla Carvalho
    Heliyon.2019; 5(11): e02753.     CrossRef
  • Ultrasensitive cytosensing based on an aptamer modified nanobiosensor with a bioconjugate: Detection of human non-small-cell lung cancer cells
    Tanveer A. Mir, Jang-Hee Yoon, N.G. Gurudatt, Mi-Sook Won, Yoon-Bo Shim
    Biosensors and Bioelectronics.2015; 74: 594.     CrossRef
  • Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma
    Su-Mi Kim, Sun-Ju Oh, Bang Hur
    Korean Journal of Pathology.2012; 46(5): 429.     CrossRef
  • MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer
    Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa, Fazlul H. Sarkar
    PLoS ONE.2012; 7(11): e49251.     CrossRef
  • Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma
    ILSEON HWANG, YU NA KANG, JIN YOUNG KIM, YOUNG ROK DO, HONG SUK SONG, KEON UK PARK
    Experimental and Therapeutic Medicine.2012; 4(2): 311.     CrossRef
Clinicopathological Significance of Invasive Ductal Carcinoma with High Prevalence of CD44(+)/CD24(-/low) Tumor Cells in Breast Cancer.
Ji Youn Sung, Gou Young Kim, Yong Koo Park, Juhie Lee, Youn Wha Kim, Sung Jig Lim
Korean J Pathol. 2010;44(4):390-396.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.390
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AbstractAbstract PDF
BACKGROUND
Epithelial tumor cells with a CD44(+)/CD24(-/low) immunoprofile may have the ability to cause breast cancer. We studied these cells and their clinicopathological significance.
METHODS
The clinicopathologic findings of 100 invasive ductal carcinoma (IDC) cases and 45 ductal carcinoma in situ (DCIS) cases were reviewed. CD44(+)/CD24(-/low) tumor cells were identified by immunohistochemistry, and their clinicopathological implications in IDC and DCIS were analyzed.
RESULTS
IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells was significantly associated with larger mass, higher grade, estrogen receptor (ER) negativity, and tumor cells with a higher frequency of metastasis. The proportion of CD44(+)/CD24(-/low) tumor cells in IDC, and its DCIS components was not significantly different, whereas the proportion of CD44(+)/CD24(-/low) tumor cells was higher in DCIS than in the DCIS component of IDC (p < 0.001).
CONCLUSIONS
IDC with a high prevalence of CD44(+)/CD24(-/low) tumor cells might correlate with aggressive features, such as ER and higher grades. Moreover, the proportion of CD44(+)/CD24(-/low) tumor cells in the DCIS components of IDC and DCIS might harbor different biology, which may lead to differences in cancer progression and early carcinogenesis.

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  • CD44 Marks Dormant Tumor Cells After HER2 Inhibition in Breast Cancer Cells
    Carla Vargas, Adam Aguirre-Ducler, Karina Cereceda, Sebastián Quijada, Nicolás Escobar-Gómez, Rodrigo L. Castillo, Matías Escobar-Aguirre
    International Journal of Molecular Sciences.2025; 26(10): 4907.     CrossRef
  • Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression
    Yoon Seok Kim, Min Jung Jung, Dong Won Ryu, Chung Han Lee
    Journal of Breast Cancer.2014; 17(2): 121.     CrossRef
  • CD44/CD24 as potential prognostic markers in node-positive invasive ductal breast cancer patients treated with adjuvant chemotherapy
    Agnieszka Adamczyk, Joanna A. Niemiec, Aleksandra Ambicka, Anna Mucha-Małecka, Jerzy Mituś, Janusz Ryś
    Journal of Molecular Histology.2014; 45(1): 35.     CrossRef
Expression of Carbonic Anhydrase IX Correlates with Histologic Grade and Metastasis in Osteosarcoma.
Hye Rim Park, Jinwon Seo, Patrizia Bacchini, Franco Bertoni, Yong Koo Park
Korean J Pathol. 2010;44(4):384-389.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.384
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AbstractAbstract PDF
BACKGROUND
Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients.
METHODS
We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis.
RESULTS
Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), and younger age (p = 0.0140). However, the overall survival rate was not significantly correlated with gender, tumor size, or American Joint Committee on Cancer stage.
CONCLUSIONS
CA9 expression is a frequent and tumor-specific event in osteosarcoma. CA9 expression is associated with higher grade tumors, metastasis and poor prognosis for the osteosarcoma patients.

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  • The reducing effect of TNF-α on carbonic anhydrase III gene expression in colon carcinoma and osteosarcoma cells
    Sümeyye Aydoğan Türkoğlu, Derya Okuyan, Feray Köçkar
    Cytotechnology.2025;[Epub]     CrossRef
Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1alpha in Oral Squamous Cell Carcinomas.
Sook Hee Hong, Sang Young Roh, Yoon Ho Ko, Hye Sung Won, Myung Ah Lee, In Sook Woo, Jae Ho Byun, Jin Hyoung Kang, Young Seon Hong, Chan Kwon Jung, Yeon Sil Kim, Young Hoon Ju, Min Sik Kim
Korean J Pathol. 2010;44(4):360-369.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.360
  • 4,815 View
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  • 1 Crossref
AbstractAbstract PDF
BACKGROUND
Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)-1alpha and prognosis.
METHODS
We performed immunohistochemical staining of HIF-1alpha, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection.
RESULTS
High reactivity of HIF-1alpha, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026).
CONCLUSIONS
Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1alpha may be independent prognostic factors in patients with oral SCC.

Citations

Citations to this article as recorded by  
  • Glucose transporter 1 (GLUT1) of anaerobic glycolysis as predictive and prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer
    Byoung Yong Shim, Ji-Han Jung, Kang-Moon Lee, Hyung-Jin Kim, Sook Hee Hong, Sung Hwan Kim, Der Sheng Sun, Hyeon-Min Cho
    International Journal of Colorectal Disease.2013; 28(3): 375.     CrossRef
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