Journal of Pathology and Translational Medicine

Original Articles

Single-center study on clinicopathological and typical molecular pathologic features of metastatic brain tumor: Su Hwa Kim, Young Suk Lee, Sung Hak Lee, Yeoun Eun Sung, Ahwon Lee, Jun Kang, Jae-Sung Park, Sin Soo Jeun, Youn Soo Lee; J Pathol Transl Med. 2023;57(4):217-231. Published online July 11, 2023; DOI: https://doi.org/10.4132/jptm.2023.06.10

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Abstract PDF: Background
The metastatic brain tumor is the most common brain tumor. The aim of this study was to demonstrate the clinicopathological and molecular pathologic features of brain metastases (BM).
Methods
A total of 269 patients were diagnosed with BM through surgical resection at Seoul St. Mary’s Hospital from January 2010 to March 2020. We reviewed the clinicopathological features and molecular status of primary and metastatic brain tissues using immunohistochemistry and molecular pathology results.
Results
Among 269 patients, 139 males and 130 females were included. The median age of primary tumor was 58 years (range, 13 to 87 years) and 86 patients (32.0%) had BM at initial presentation. Median BM free interval was 28.0 months (range, 1 to 286 months). The most frequent primary site was lung 46.5% (125/269), and followed by breast 15.6% (42/269), colorectum 10.0% (27/269). Epidermal growth factor receptor (EGFR) mutation was found in 50.8% (32/63) and 58.0% (40/69) of lung primary and BM, respectively. In both breast primary and breast cancer with BM, luminal B was the most frequent subtype at 37.9% (11/29) and 42.9% (18/42), respectively, followed by human epidermal growth factor receptor 2 with 31.0% (9/29) and 33.3% (14/42). Triple-negative was 20.7% (6/29) and 16.7% (7/42), and luminal A was 10.3% (3/29) and 7.1% (3/42) of breast primary and BM, respectively. In colorectal primary and colorectal cancer with BM, KRAS mutation was found in 76.9% (10/13) and 66.7% (2/3), respectively.
Conclusions
We report the clinicopathological and molecular pathologic features of BM that can provide useful information for understanding the pathogenesis of metastasis and for clinical trials based on the tumor’s molecular pathology.

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

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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.

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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

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

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Abstract 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.

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Review

Molecular characteristics of meningiomas: Young Suk Lee, Youn Soo Lee; J Pathol Transl Med. 2020;54(1):45-63. Published online January 15, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.05

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Abstract PDF

Meningioma is the most common primary intracranial tumor in adults. The grading of meningioma is based on World Health Organization criteria, which rely on histopathological features alone. This grading system is unable to conclusively predict the clinical behavior of these tumors (i.e., recurrence or prognosis in benign or atypical grades). Advances in molecular techniques over the last decade that include genomic and epigenomic data associated with meningiomas have been used to identify genetic biomarkers that can predict tumor behavior. This review summarizes the molecular characteristics of meningioma using genetic and epigenetic biomarkers. Molecular alterations that can predict meningioma behavior may be integrated into the upcoming World Health Organization grading system.

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Original Article

PD-L1 Expression and Combined Status of PD-L1/PD-1–Positive Tumor Infiltrating Mononuclear Cell Density Predict Prognosis in Glioblastoma Patients: Jiheun Han, Yongkil Hong, Youn Soo Lee; J Pathol Transl Med. 2017;51(1):40-48. Published online December 15, 2016; DOI: https://doi.org/10.4132/jptm.2016.08.31

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Abstract PDF

Background
Programmed death ligand 1 (PD-L1) in tumor cells is known to promote immune escape of cancer by interacting with programmed cell death 1 (PD-1) in tumor infiltrating immune cells. Immunotherapy targeting these molecules is emerging as a new strategy for the treatment of glioblastoma (GBM). Understanding the relationship between the PD-L1/PD-1 axis and prognosis in GBM patients may be helpful to predict the effects of immunotherapy.
Methods
PD-L1 expression and PD-1–positive tumor infiltrating mononuclear cell (PD-1+tumor infiltrating mononuclear cell [TIMC]) density were evaluated using tissue microarray containing 54 GBM cases by immunohistochemical analysis; the associations with patient clinical outcomes were evaluated.
Results
PD-L1 expression and high PD-1+TIMC density were observed in 31.5% and 50% of GBM cases, respectively. High expression of PD-L1 in tumor cells was an independent and significant predictive factor for worse overall survival (OS; hazard ratio, 4.958; p = .007) but was not a significant factor in disease-free survival (DFS). PD-1+TIMC density was not correlated with OS or DFS. When patients were classified based on PD-1 expression and PD-1+TIMC density, patients with PD-L1+/PD-1+TIMC low status had the shortest OS (13 months, p = .009) and DFS (7 months, p = .053).
Conclusions
PD-L1 expression in GBM was an independent prognostic factor for poor OS. In addition, combined status of PD-L1 expression and PD-1+TIMC density also predicted patient outcomes, suggesting that the therapeutic role of the PD-1/PD-L1 axis should be considered in the context of GBM immunity.

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Brief Case Report

Human Papillomavirus Infection–Associated Adenoid Cystic Carcinoma of the Hard Palate: Arthur Minwoo Chung, Dong Il Sun, Eun Sun Jung, Youn Soo Lee; J Pathol Transl Med. 2017;51(3):329-331. Published online December 5, 2016; DOI: https://doi.org/10.4132/jptm.2016.07.07

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Adenoid Cystic Carcinoma of the Skull Base: Response to Radiation Therapy and Outcomes in a Retrospective Case Series
Shekhar K. Gadkaree, Anuraag S. Parikh, Alejandro I. Rodarte, Ashton Lehmann, Stacey T. Gray, Derrick T. Lin
Journal of Neurological Surgery Part B: Skull Base.2020; 81(05): 505. CrossRef

Original Articles

The Predictive Value of Pathologic Features in Pituitary Adenoma and Correlation with Pituitary Adenoma Recurrence: Jee Soon Kim, Youn Soo Lee, Min Jung Jung, Yong Kil Hong; J Pathol Transl Med. 2016;50(6):419-425. Published online October 6, 2016; DOI: https://doi.org/10.4132/jptm.2016.06.30

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Abstract PDF

Background
The 2004 World Health Organization classification introduced atypical pituitary adenoma (aPA), which was equivocally defined as invasion with increased mitotic activity that had a Ki-67 labeling index (LI) greater than 3%, and extensive p53 immunoreactivity. However, aPAs that exhibit all of these features are rare and the predictive value for recurrence in pituitary adenomas (PAs) remains uncertain. Thus, we sought to characterize pathological features of PAs that correlated with recurrence.
Methods
One hundred and sixty-seven cases of surgically resected PA or aPA were retrieved from 2011 to 2013 in Seoul St. Mary’s Hospital. Among them, 28 cases were confirmed to be recurrent, based on pathologic or radiologic examination. The pathologic characteristics including mitosis, invasion, Ki-67 LI and p53 immunoreactivity were analyzed in relation to recurrence.
Results
Analysis of the pathologic features indicated that only Ki-67 LI over 3% was significantly associated with tumor recurrence (p = .02). The cases with at least one pathologic feature showed significantly higher recurrence rates (p < .01). Analysis indicated that cases with two pathologic features, Ki-67 LI over 3% and extensive p53 immunoreactivity 20% or more, were significantly associated with tumor recurrence (p < .01).
Conclusions
Based on these results, PA tumor recurrence can be predicted by using mitosis, invasion, Ki-67 LI (3%), or extensive p53 immunoreactivity (≥ 20%). Assessment of these features is recommended for PA diagnosis for more accurate prediction of recurrence.

Citations

Citations to this article as recorded by

The Value of ER∝ in the Prognosis of GH- and PRL-Secreting PitNETs: Clinicopathological Correlations
Roxana-Ioana Dumitriu-Stan, Iulia-Florentina Burcea, Valeria Nicoleta Nastase, Raluca Amalia Ceaușu, Anda Dumitrascu, Laurentiu Catalin Cocosila, Alexandra Bastian, Sabina Zurac, Marius Raica, Catalina Poiana
International Journal of Molecular Sciences.2023; 24(22): 16162. CrossRef
Ki-67/MIB-1 and Recurrence in Pituitary Adenoma
Kent Tadokoro, Colten Wolf, Joseph Toth, Cara Joyce, Meharvan Singh, Anand Germanwala, Chirag Patel
Journal of Neurological Surgery Part B: Skull Base.2022; 83(S 02): e580. CrossRef
Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas
Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim
Journal of Pathology and Translational Medicine.2022; 56(1): 22. CrossRef
A Preoperative MRI-Based Radiomics-Clinicopathological Classifier to Predict the Recurrence of Pituitary Macroadenoma Within 5 Years
Yu Zhang, Yuqi Luo, Xin Kong, Tao Wan, Yunling Long, Jun Ma
Frontiers in Neurology.2022;[Epub] CrossRef
Endoscopic Endonasal Pituitary Surgery For Nonfunctioning Pituitary Adenomas: Long-Term Outcomes and Management of Recurrent Tumors
Anne-Laure Bernat, Pénélope Troude, Stefano Maria Priola, Ahmad Elsawy, Faisal Farrash, Ozgur Mete, Shereen Ezzat, Sylvia L. Asa, John De Almeida, Allan Vescan, Eric Monteiro, Joao Paulo Almeida, Gelareh Mohammed Zadeh, Fred Gentili
World Neurosurgery.2021; 146: e341. CrossRef
A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study
Xiangming Cai, Junhao Zhu, Jin Yang, Chao Tang, Feng Yuan, Zixiang Cong, Chiyuan Ma
Frontiers in Oncology.2021;[Epub] CrossRef
Comparative Proteomic Study Shows the Expression of Hint-1 in Pituitary Adenomas
Carolina Carrillo-Najar, Daniel Rembao-Bojórquez, Martha L. Tena-Suck, Sergio Zavala-Vega, Noemí Gelista-Herrera, Miguel A. Ramos-Peek, Juan L. Gómez-Amador, Febe Cazares-Raga, Fidel de la Cruz Hernández-Hernández, Alma Ortiz-Plata
Diagnostics.2021; 11(2): 330. CrossRef
Prediction of recurrence in solid nonfunctioning pituitary macroadenomas: additional benefits of diffusion-weighted MR imaging
Ching-Chung Ko, Tai-Yuan Chen, Sher-Wei Lim, Yu-Ting Kuo, Te-Chang Wu, Jeon-Hor Chen
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Pituitary tumors: epidemiology and clinical presentation spectrum
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Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature
E. Guadagno, E. D’Avella, P. Cappabianca, A. Colao, M. Del Basso De Caro
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Study of Simple Immunohistochemical Cytocolorimetric Assay Application for More Accurate Assessment of Prognosis in Patients with Pituitary Adenomas
Pavel V. Nikitin, Marina V. Ryzhova, Lyudmila V. Shishkina, Svetlana V. Shugay, Irina V. Zubova
World Neurosurgery.2019; 122: e1047. CrossRef
The Prognostic Roles of the Ki-67 Proliferation Index, P53 Expression, Mitotic Index, and Radiological Tumor Invasion in Pituitary Adenomas
Rovshan Hasanov, Berna İmge Aydoğan, Saba Kiremitçi, Esra Erden, Sevim Güllü
Endocrine Pathology.2019; 30(1): 49. CrossRef
Residual Tumor Confers a 10-Fold Increased Risk of Regrowth in Clinically Nonfunctioning Pituitary Tumors
Jelena Maletkovic, Asmaa Dabbagh, Dongyun Zhang, Abdul Zahid, Marvin Bergsneider, Marilene B Wang, Michael Linetsky, Noriko Salamon, William H Yong, Harry V Vinters, Anthony P Heaney
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Atypical pituitary adenoma: a clinicopathologic case series
Martin J. Rutkowski, Ryan M. Alward, Rebecca Chen, Jeffrey Wagner, Arman Jahangiri, Derek G. Southwell, Sandeep Kunwar, Lewis Blevins, Han Lee, Manish K. Aghi
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Both invasiveness and proliferation criteria predict recurrence of non-functioning pituitary macroadenomas after surgery: a retrospective analysis of a monocentric cohort of 120 patients
Julie Lelotte, Anne Mourin, Edward Fomekong, Alex Michotte, Christian Raftopoulos, Dominique Maiter
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Letter to the Editor. Atypical pituitary adenoma
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Histologic Disorderliness in the Arrangement of Tumor Cells as an Objective Measure of Tumor Differentiation: Sungwook Suh, Gyeongsin Park, Young Sub Lee, Yosep Chong, Youn Soo Lee, Yeong Jin Choi; Korean J Pathol. 2014;48(5):339-345. Published online October 27, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.5.339

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Abstract PDF: Background: Inter-observer and intra-observer variation in histologic tumor grading are well documented. To determine whether histologic disorderliness in the arrangement of tumor cells may serve as an objective criterion for grading, we tested the hypothesis the degree of disorderliness is related to the degree of tumor differentiation on which tumor grading is primarily based. Methods: Borrowing from the statistical thermodynamic definition of entropy, we defined a novel mathematical formula to compute the relative degree of histologic disorderliness of tumor cells. We then analyzed a total of 51 photomicrographs of normal colorectal mucosa and colorectal adenocarcinoma with varying degrees of differentiation using our formula. Results: A one-way analysis of variance followed by post hoc pairwise comparisons using Bonferroni correction indicated that the mean disorderliness score was the lowest for the normal colorectal mucosa and increased with decreasing tumor differentiation. Conclusions: Disorderliness, a pathologic feature of malignant tumors that originate from highly organized structures is useful as an objective tumor grading proxy in the field of digital pathology.

Classic Papillary Thyroid Carcinoma with Tall Cell Features and Tall Cell Variant Have Similar Clinicopathologic Features: Woo Jin Oh, Young Sub Lee, Uiju Cho, Ja Seong Bae, Sohee Lee, Min Hee Kim, Dong Jun Lim, Gyeong Sin Park, Youn Soo Lee, Chan Kwon Jung; Korean J Pathol. 2014;48(3):201-208. Published online June 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.201

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Abstract PDF

Background

The tall cell variant of papillary thyroid carcinoma (TCVPTC) is more aggressive than classic papillary thyroid carcinoma (PTC), but the percentage of tall cells needed to diagnose TCVPTC remains controversial. In addition, little is known about the clinicopathologic features of classic PTC with tall cell features (TCF).

Methods

We retrospectively selected and reviewed the clinicopathologic features and presence of the BRAF mutation in 203 cases of classic PTC, 149 cases of classic PTC with TCF, and 95 cases of TCVPTCs, which were defined as PTCs having <10%, 10-50%, and ≥50% tall cells, respectively.

Results

TCVPTCs and classic PTCs with TCF did not vary significantly in clinicopathologic characteristics such as pathologic (p) T stage, extrathyroidal extension, pN stage, lateral lymph node metastasis, or BRAF mutations; however, these features differed significantly in TCVPTCs and classic PTCs with TCF in comparison to classic PTCs. Similar results were obtained in a subanalysis of patients with microcarcinomas (≤1.0 cm in size).

Conclusions

Classic PTCs with TCF showed a similar BRAF mutation rate and clinicopathologic features to TCVPTCs, but more aggressive characteristics than classic PTCs.

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Endocrine Connections.2018; 7(12): R286. CrossRef
TERT Promoter Mutation in an Aggressive Cribriform Morular Variant of Papillary Thyroid Carcinoma
Eun Ji Oh, Sohee Lee, Ja Seong Bae, Yourha Kim, Sora Jeon, Chan Kwon Jung
Endocrine Pathology.2017; 28(1): 49. CrossRef
Update on the cytologic features of papillary thyroid carcinoma variants
Marc Pusztaszeri, Manon Auger
Diagnostic Cytopathology.2017; 45(8): 714. CrossRef
Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive f
Uiju Cho, Ozgur Mete, Min-Hee Kim, Ja Seong Bae, Chan Kwon Jung
Modern Pathology.2017; 30(6): 810. CrossRef
BRAF-positive paucicellular variant of anaplastic carcinoma in the presence of tall cell variant papillary thyroid cancer
O. V. Dolzhansky, E. M. Paltseva, D. N. Khmelkova, F. A. Konovalov, I. V. Kanivets, A. V. Lavrov, D. V. Pyankov, S. A. Korostelev, O. A. Levendyuk, V. M. Pominalnaya, D. N. Fedorov
Arkhiv patologii.2017; 79(3): 27. CrossRef
A comparison of the clinicopathological features and prognoses of the classical and the tall cell variant of papillary thyroid cancer: a meta-analysis
Zeming Liu, Wen Zeng, Tianwen Chen, Yawen Guo, Chao Zhang, Chunping Liu, Tao Huang
Oncotarget.2017; 8(4): 6222. CrossRef
Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation
Ja Seong Bae, Yourha Kim, Sora Jeon, Se Hee Kim, Tae Jung Kim, Sohee Lee, Min-Hee Kim, Dong Jun Lim, Youn Soo Lee, Chan Kwon Jung
Diagnostic Pathology.2016;[Epub] CrossRef
Tall cell variant of papillary thyroid carcinoma: current evidence on clinicopathologic features and molecular biology
Xiaofei Wang, Wenli Cheng, Chongqing Liu, Jingdong Li
Oncotarget.2016; 7(26): 40792. CrossRef
The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto’s Thyroiditis
Min-kyung Yeo, Ja Seong Bae, Sohee Lee, Min-Hee Kim, Dong-Jun Lim, Youn Soo Lee, Chan Kwon Jung
International Journal of Endocrinology.2015; 2015: 1. CrossRef
BRAF Immunohistochemistry Using Clone VE1 is Strongly Concordant with BRAFV600E Mutation Test in Papillary Thyroid Carcinoma
Jung-Soo Pyo, Jin Hee Sohn, Guhyun Kang
Endocrine Pathology.2015; 26(3): 211. CrossRef
Pathologie de la thyroïde. Cas no 3. Carcinome papillaire de la thyroïde, variante à cellules hautes
Emmanuelle Leteurtre
Annales de Pathologie.2015; 35(5): 402. CrossRef

Brief Case Report

Esophageal Squamous Cell Carcinoma In Situ Overlying Leiomyoma Mimicking Invasive Cancer: A Brief Case Report: Woo Jin Oh, Eun Jung Lee, Youn Soo Lee, Tae-Jung Kim; Korean J Pathol. 2014;48(2):162-163. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.162

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Esophageal squamous cell carcinoma or high-grade dysplasia overlying leiomyoma, rare but not to be neglected
Changyuan Guo, Dan Liu, Yong Liu, Lei Guo, Lulu Rong, Guiqi Wang, Ning Lu, Liyan Xue
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Esophageal leiomyoma and simultaneous overlying squamous cell carcinoma: a case report and review of the literature
Saadat Mehrabi, Mohammad Javad Yavari Barhaghtalab, Safoora Hejazinia, Hossein Saedi
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Original Articles

Microtubule-Associated Protein Tau, α-Tubulin and βIII-Tubulin Expression in Breast Cancer: Soyoung Im, Changyoung Yoo, Ji-Han Jung, Ye-Won Jeon, Young Jin Suh, Youn Soo Lee, Hyun Joo Choi; Korean J Pathol. 2013;47(6):534-540. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.534

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Abstract PDF

Background

The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment.

Methods

Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival.

Results

Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049).

Conclusions

Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.

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Tubulin Isotypes: Emerging Roles in Defining Cancer Stem Cell Niche
Tessy Thomas Maliekal, Dhrishya Dharmapal, Suparna Sengupta
Frontiers in Immunology.2022;[Epub] CrossRef
RAD6 inhibition enhances paclitaxel sensitivity of triple negative breast cancer cells by aggravating mitotic spindle damage
Brittany M. Haynes, Kristen Cunningham, Malathy P. V. Shekhar
BMC Cancer.2022;[Epub] CrossRef
Influence of Paclitaxel and Doxorubicin Therapy of ßIII-Tubulin, Carbonic Anhydrase IX, and Survivin in Chemically Induced Breast Cancer in Female Rat
Alena Pastornická, Silvia Rybárová, Slávka Drahošová, Jozef Mihalik, Andrea Kreheľová, Andriana Pavliuk-Karachevtseva, Ingrid Hodorová
International Journal of Molecular Sciences.2021; 22(12): 6363. CrossRef
Intelligently thermoresponsive flower-like hollow nano-ruthenium system for sustained release of nerve growth factor to inhibit hyperphosphorylation of tau and neuronal damage for the treatment of Alzheimer's disease
Hui Zhou, Youcong Gong, Yanan Liu, Anlian Huang, Xufeng Zhu, Jiawei Liu, Guanglong Yuan, Li Zhang, Ji-an Wei, Jie Liu
Biomaterials.2020; 237: 119822. CrossRef
HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells
J. R. Ribeiro, C. Schorl, N. Yano, N. Romano, K. K. Kim, R. K. Singh, R. G. Moore
Journal of Ovarian Research.2016;[Epub] CrossRef
A strategy to identify housekeeping genes suitable for analysis in breast cancer diseases
Tatiana M. Tilli, Cláudio da Silva Castro, Jack A. Tuszynski, Nicolas Carels
BMC Genomics.2016;[Epub] CrossRef
Increased expression of αTubulin is associated with poor prognosis in patients with pancreatic cancer after surgical resection
Chao Lin, Guo-chao Zhao, Ya-dong Xu, Dan-song Wang, Da-yong Jin, Yuan Ji, Wen-hui Lou, Wen-chuan Wu
Oncotarget.2016; 7(37): 60657. CrossRef
Oblongifolin C inhibits metastasis by up-regulating keratin 18 and tubulins
Xiaoyu Wang, Yuanzhi Lao, Naihan Xu, Zhichao Xi, Man Wu, Hua Wang, Xiyi Li, Hongsheng Tan, Menghong Sun, Hongxi Xu
Scientific Reports.2015;[Epub] CrossRef
Regulation of human MAPT gene expression
Marie-Laure Caillet-Boudin, Luc Buée, Nicolas Sergeant, Bruno Lefebvre
Molecular Neurodegeneration.2015;[Epub] CrossRef

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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Abstract 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.

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High-Risk Human Papillomavirus Detection via Cobas® 4800 and REBA HPV-ID® Assays
Sasiprapa Liewchalermwong, Shina Oranratanaphan, Wichai Termrungruanglert, Surang Triratanachat, Patou Tantbirojn, Nakarin Kitkumthorn, Parvapan Bhattarakosol, Arkom Chaiwongkot
Viruses.2022; 14(12): 2713. CrossRef
Evaluation of nuclear chromatin using grayscale intensity and thresholded percentage area in liquid‐based cervical cytology
Hyekyung Lee, Myungein Han, Taejo Yoo, Chanho Jung, Hyun‐Jin Son, Migyung Cho
Diagnostic Cytopathology.2018; 46(5): 384. CrossRef
Comparison of EASYPREP® and SurePath® in thyroid fine‐needle aspiration
Yosep Chong, Ki Hyun Baek, Jee Young Kim, Tae‐Jung Kim, Eun Jung Lee, Chang Suk Kang
Diagnostic Cytopathology.2016; 44(4): 283. CrossRef

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II): Jin Hee Sohn, Gyungyub Gong, Kyu Rae Kim, Chang Suk Kang, Youn Soo Lee, Jin Man Kim, Woo Hee Jung, Kwang Sun Suh; Korean J Pathol. 2012;46(3):226-232. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.226

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Abstract PDF

Background

Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts.

Methods

As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP.

Results

Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature.

Conclusions

Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

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Update on the Proposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I-2)
Eun Sun Jung, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Won Ae Lee, Hee Eun Lee, Sunhoo Park, Jin Hee Sohn, So-Young Jin
Korean Journal of Pathology.2012; 46(5): 443. CrossRef
A Proposal for Creating a Guideline for Cancer Registration of the Fibromatosis, PEComa Group, Malignant LymphomaIn Situand Dendritic Cell Tumors (III)
Changyoung Yoo, Chang Suk Kang, Yoon La Choi, Hye Yoon Kang, Jin Man Kim, Young Hye Koh, Joo Hee Lee, Seung Sook Lee, In Sun Kim, Dong Hoon Kim, Yong Ku Park, Jin Hee Sohn
Korean Journal of Pathology.2012; 46(5): 436. CrossRef

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

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Abstract 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
Indian Journal of Surgical Oncology.2021; 12(S1): 134. CrossRef
In situ hybridization for high risk HPV E6/E7 mRNA in oropharyngeal squamous cell carcinoma
Krish Suresh, Parth V. Shah, Sydney Coates, Borislav A. Alexiev, Sandeep Samant
American Journal of Otolaryngology.2021; 42(1): 102782. CrossRef
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
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
Archives of Pathology & Laboratory Medicine.2018; 142(5): 559. CrossRef
Detection of HPV infection in head and neck cancers: Promise and pitfalls in the last ten years: A meta-analysis
Carolin G�tz, Clara Bischof, Klaus-Dietrich Wolff, Andreas Kolk
Molecular and Clinical Oncology.2018;[Epub] CrossRef
Frequent hepatocyte growth factor overexpression and low frequency of c-Met gene amplification in human papillomavirus–negative tonsillar squamous cell carcinoma and their prognostic significances
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
Human Pathology.2014; 45(7): 1327. CrossRef
Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma
Yoon Ho Ko, Hye Sung Won, Der Sheng Sun, Ho Jung An, Eun Kyoung Jeon, Min Sik Kim, Han Hong Lee, Jin Hyoung Kang, Chan Kwon Jung
Pathology International.2014; 64(10): 499. CrossRef
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 Journal of Pathology.2013; 47(2): 148. CrossRef

Alteration of Apoptosis-Related Proteins (Apaf-1, Caspase-9, Bcl-2, p53, and Survivin) According to Malignant Progression in Cutaneous Melanocytic Lesions.: Yeo Ju Kang, Ji Han Jung, Kwnag Il Yim, Kyo Young Lee, Youn Soo Lee, Seok Jin Kang, Chang Suk Kang, Si Yong Kim; Korean J Pathol. 2011;45(3):247-253.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.247

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Abstract PDF: BACKGROUND
Apoptosis protease activating factor-1 (Apaf-1), caspase-9, Bcl-2, p53, and survivin are important factors in the pathway of apoptosis, but their clinicopathologic significance remains unclear in human cutaneous melanoma. We investigated the expression of these proteins and their clinical value in human cutaneous melanocytic lesions.
METHODS
We performed an immunohistochemical analysis to examine the expression and distribution of Apaf-1, caspase-9, Bcl-2, p53, and survivin in 36 cases of malignant melanoma (22 cases of primary melanoma and 14 cases of metastatic melanoma) and 41 cases of melanocytic nevus.
RESULTS
The expression of p53 was significantly higher in malignant melanoma than in melanocytic nevus (p<0.01), however the expressions of Apaf-1 and caspase-9 were significantly lower in malignant melanoma compared with melanocytic nevus (p<0.01 and p=0.027, respectively). Also, there was a significant difference for Bcl-2 staining between primary melanomas and metastatic lesions (p=0.004). Nuclear staining for survivin were absent in nevus, but were positive in 14 of 36 melanomas (p<0.01).
CONCLUSIONS
The altered expression of Apaf-1, caspase-9, p53, and survivin are considered to be related to malignant progression in human cutaneous melanocytic lesions. Loss of Bcl-2 can be considered as a prognostic marker of malignant melanomas.

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