Journal of Pathology and Translational Medicine

Correspondence

Erratum: Breast fine-needle aspiration cytology in the era of core-needle biopsy: what is its role?: Ahrong Kim, Hyun Jung Lee, Jee Yeon Kim; J Pathol Transl Med. 2025;59(2):147-147. Published online March 14, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.01.r; Corrects: J Pathol Transl Med 2025;59(1):26

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Review

Breast fine-needle aspiration cytology in the era of core-needle biopsy: what is its role?: Ahrong Kim, Hyun Jung Lee, Jee Yeon Kim; J Pathol Transl Med. 2025;59(1):26-38. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.11.01; Correction in: J Pathol Transl Med 2025;59(2):147

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Fine-needle aspiration cytology (FNAC) has long been recognized as a minimally invasive, cost-effective, and reliable diagnostic tool for breast lesions. However, with the advent of core-needle biopsy (CNB), the role of FNAC has diminished in some clinical settings. This review aims to re-evaluate the diagnostic value of FNAC in the current era, focusing on its complementary use alongside CNB, the adoption of new approaches such as the International Academy of Cytology Yokohama System, and the implementation of rapid on-site evaluation to reduce inadequate sample rates. Advances in liquid-based cytology, receptor expression testing, molecular diagnostics, and artificial intelligence are discussed, highlighting their potential to enhance the diagnostic accuracy of FNAC. Despite challenges, FNAC remains a valuable diagnostic method, particularly in low-resource settings and specific clinical scenarios, and its role continues to evolve with technology.

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Bulk-lysis protocols as a sensitive method for investigation of circulating CK19 cells in the peripheral blood of patients with breast cancer by flow cytometry
Daniella Serafin Couto Vieira, Laura Otto Walter, Maria Eduarda Cunha da Silva, Lisandra de Oliveira Silva, Heloísa Zorzi Costa, Chandra Chiappin Cardoso, Fernando Carlos de Lander Schmitt, Maria Cláudia Santos-Silva
Analytical Methods.2025; 17(23): 4771. CrossRef

Original Article

Comparison of tissue-based and plasma-based testing for EGFR mutation in non–small cell lung cancer patients: Yoon Kyung Kang, Dong Hoon Shin, Joon Young Park, Chung Su Hwang, Hyun Jung Lee, Jung Hee Lee, Jee Yeon Kim, JooYoung Na; J Pathol Transl Med. 2025;59(1):60-67. Published online January 15, 2025; DOI: https://doi.org/10.4132/jptm.2024.10.01

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Abstract PDF: Background
Epidermal growth factor receptor (EGFR) gene mutation testing is crucial for the administration of tyrosine kinase inhibitors to treat non–small cell lung cancer. In addition to traditional tissue-based tests, liquid biopsies using plasma are increasingly utilized, particularly for detecting T790M mutations. This study compared tissue- and plasma-based EGFR testing methods.
Methods
A total of 248 patients were tested for EGFR mutations using tissue and plasma samples from 2018 to 2023 at Pusan National University Yangsan Hospital. Tissue tests were performed using PANAmutyper, and plasma tests were performed using the Cobas EGFR Mutation Test v2.
Results
All 248 patients underwent tissue-based EGFR testing, and 245 (98.8%) showed positive results. Of the 408 plasma tests, 237 (58.1%) were positive. For the T790M mutation, tissue biopsies were performed 87 times in 69 patients, and 30 positive cases (38.6%) were detected. Plasma testing for the T790M mutation was conducted 333 times in 207 patients, yielding 62 positive results (18.6%). Of these, 57 (27.5%) were confirmed to have the mutation via plasma testing. Combined tissue and plasma tests for the T790M mutation were positive in nine patients (13.4%), while 17 (25.4%) were positive in tissue only and 12 (17.9%) in plasma only. This mutation was not detected in 28 patients (43.3%).
Conclusions
Although the tissue- and plasma-based tests showed a sensitivity of 37.3% and 32.8%, respectively, combined testing increased the detection rate to 56.7%. Thus, neither test demonstrated superiority, rather, they were complementary.

Case Study

Primary testicular carcinoid tumor with marked lymphovascular invasion: Hyun Jung Lee, Joon Young Park, So Young Kim, Chung Su Hwang, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim; J Pathol Transl Med. 2021;55(6):410-414. Published online October 20, 2021; DOI: https://doi.org/10.4132/jptm.2021.09.11

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Abstract PDF

Testicular carcinoid tumors are very rare, accounting for less than 1% of all testicular tumors. We report a rare case of a testicular carcinoid tumor with extensive lymphatic invasion. A 42-year-old man presented with a painless, enlarged right testicular mass. There was no history of injury or discomfort in this region. Right radical orchiectomy was performed, which showed a well-defined, non-encapsulated solid white mass with calcification (7.0 × 4.5 × 3.5 cm) and absence of cystic components. Microscopic examination using hematoxylin and eosin staining of the tumor sections identified organoid, trabecular, and solid patterns with rosette formation. Extensive multifocal lymphatic invasion was observed. Immunohistochemistry was positive for synaptophysin, chromogranin, and CD56. Testicular carcinoid tumors usually show good prognoses; however, there was extensive lymphovascular invasion in this case. Thus, in the case of unusual presentation of the disease, close follow-up is necessary.

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Testicular Primary Well-Differentiated Neuroendocrine Tumor: Clinicopathologic, Immunohistochemical, and Molecular Characterization of Two Patients
Liwei Jia, Bo Zhang, Daniel Shen, Prasad R. Koduru
International Journal of Surgical Pathology.2024; 32(8): 1574. CrossRef

Original Article

A multicenter study of interobserver variability in pathologic diagnosis of papillary breast lesions on core needle biopsy with WHO classification: Hye Ju Kang, Sun Young Kwon, Ahrong Kim, Woo Gyeong Kim, Eun Kyung Kim, Ae Ree Kim, Chungyeul Kim, Soo Kee Min, So Young Park, Sun Hee Sung, Hye Kyoung Yoon, Ahwon Lee, Ji Shin Lee, Hyang Im Lee, Ho Chang Lee, Sung Chul Lim, Sun Young Jun, Min Jung Jung, Chang Won Jung, Soo Youn Cho, Eun Yoon Cho, Hye Jeong Choi, So Yeon Park, Jee Yeon Kim, In Ae Park, Youngmee Kwon; J Pathol Transl Med. 2021;55(6):380-387. Published online October 6, 2021; DOI: https://doi.org/10.4132/jptm.2021.07.29

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Abstract PDF Supplementary Material

Background
Papillary breast lesions (PBLs) comprise diverse entities from benign and atypical lesions to malignant tumors. Although PBLs are characterized by a papillary growth pattern, it is challenging to achieve high diagnostic accuracy and reproducibility. Thus, we investigated the diagnostic reproducibility of PBLs in core needle biopsy (CNB) specimens with World Health Organization (WHO) classification.
Methods
Diagnostic reproducibility was assessed using interobserver variability (kappa value, κ) and agreement rate in the pathologic diagnosis of 60 PBL cases on CNB among 20 breast pathologists affiliated with 20 medical institutions in Korea. This analysis was performed using hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for cytokeratin 5 (CK5) and p63. The pathologic diagnosis of PBLs was based on WHO classification, which was used to establish simple classifications (4-tier, 3-tier, and 2-tier).
Results
On WHO classification, H&E staining exhibited ‘fair agreement’ (κ = 0.21) with a 47.0% agreement rate. Simple classifications presented improvement in interobserver variability and agreement rate. IHC staining increased the kappa value and agreement rate in all the classifications. Despite IHC staining, the encapsulated/solid papillary carcinoma (EPC/SPC) subgroup (κ = 0.16) exhibited lower agreement compared to the non-EPC/SPC subgroup (κ = 0.35) with WHO classification, which was similar to the results of any other classification systems.
Conclusions
Although the use of IHC staining for CK5 and p63 increased the diagnostic agreement of PBLs in CNB specimens, WHO classification exhibited a higher discordance rate compared to any other classifications. Therefore, this result warrants further intensive consensus studies to improve the diagnostic reproducibility of PBLs with WHO classification.

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Beyond the benign: A rare case report of myxoid pleomorphic liposarcoma
Arslan Ahmad, Muhammad Ammar, Muhammad Hasnain Saleem Choudary, Muhammad Nouman Sadiq, Rana Uzair Ahmad, Nouman Aziz
Radiology Case Reports.2025; 20(5): 2500. CrossRef
Invasive papillary carcinoma of the breast
Shijing Wang, Qingfu Zhang, Xiaoyun Mao
Frontiers in Oncology.2024;[Epub] CrossRef
Recommendations for Performance Evaluation of Machine Learning in Pathology: A Concept Paper From the College of American Pathologists
Matthew G. Hanna, Niels H. Olson, Mark Zarella, Rajesh C. Dash, Markus D. Herrmann, Larissa V. Furtado, Michelle N. Stram, Patricia M. Raciti, Lewis Hassell, Alex Mays, Liron Pantanowitz, Joseph S. Sirintrapun, Savitri Krishnamurthy, Anil Parwani, Giovann
Archives of Pathology & Laboratory Medicine.2024; 148(10): e335. CrossRef
Encapsulated papillary carcinoma of the breast: A single institution experience
Liang Xu, Qixin Mao, Qiuming Liu, Yufeng Gao, Lihua Luo, Chungen Guo, Wei Qu, Ningning Yan, Yali Cao
Oncology Letters.2023;[Epub] CrossRef
High-risk and selected benign breast lesions diagnosed on core needle biopsy: Evidence for and against immediate surgical excision
Aparna Harbhajanka, Hannah L. Gilmore, Benjamin C. Calhoun
Modern Pathology.2022; 35(11): 1500. CrossRef

Review

Standardized pathology report for breast cancer: Soo Youn Cho, So Yeon Park, Young Kyung Bae, Jee Yeon Kim, Eun Kyung Kim, Woo Gyeong Kim, Youngmee Kwon, Ahwon Lee, Hee Jin Lee, Ji Shin Lee, Jee Young Park, Gyungyub Gong, Hye Kyoung Yoon; J Pathol Transl Med. 2021;55(1):1-15. Published online January 11, 2021; DOI: https://doi.org/10.4132/jptm.2020.11.20

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Abstract PDF Supplementary Material

Given the recent advances in management and understanding of breast cancer, a standardized pathology report reflecting these changes is critical. To meet this need, the Breast Pathology Study Group of the Korean Society of Pathologists has developed a standardized pathology reporting format for breast cancer, consisting of ‘standard data elements,’ ‘conditional data elements,’ and a biomarker report form. The ‘standard data elements’ consist of the basic pathologic features used for prognostication, while other factors related to prognosis or diagnosis are described in the ‘conditional data elements.’ In addition to standard data elements, all recommended issues are also presented. We expect that this standardized pathology report for breast cancer will improve diagnostic concordance and communication between pathologists and clinicians, as well as between pathologists inter-institutionally.

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Adenoid Cystic Carcinoma of Breast Associated With an Incidental Radial Scar: A Cyto‐Histopathology Correlation
Rallapalli Rajyalakshmi, Valasapalli Rajani, Tanuku Sreedhar, Kollabathula Arpitha
Diagnostic Cytopathology.2026;[Epub] CrossRef
Navigating discrepancies: The assessment of residual lymphovascular invasion in breast carcinoma after neoadjuvant treatment
Anikó Kovács, Åsa Rundgren-Sellei, Gunilla Rask, Annette Bauer, Anna Bodén, Johannes van Brakel, Eugenia Colón-Cervantes, Anna Ehinger, Johan Hartman, Balazs Acs
The Breast.2025; 82: 104519. CrossRef
Residual pure intralymphatic carcinoma component only (lymphovascular tumor emboli without invasive carcinoma) after neoadjuvant chemotherapy is associated with poor outcome: Not pathologic complete response
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Matthew G. Davey, Colm O’Flaherty, Eoin F. Cleere, Aoife Nohilly, James Phelan, Evan Ronane, Aoife J. Lowery, Michael J. Kerin
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Original Articles

Prognostic Significance of CD109 Expression in Patients with Ovarian Epithelial Cancer: So Young Kim, Kyung Un Choi, Chungsu Hwang, Hyung Jung Lee, Jung Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Jae Ho Kim, Ki Hyung Kim, Dong Soo Suh, Byung Su Kwon; J Pathol Transl Med. 2019;53(4):244-252. Published online May 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.04.16

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Abstract PDF

Background
Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis.
Methods
Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy.
Results
CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001).
Conclusions
Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.

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Advances in the Study of CD109 in Tumors
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Medical Diagnosis.2024; 14(02): 167. CrossRef
Identification of CD109 in the extracellular vesicles derived from ovarian cancer stem-like cells
Ye Eun Kim, Jun Se Kim, Min Joo Shin, Seo Yul Lee, Dae Kyoung Kim, Nam-Kyung Lee, Yang Woo Kwon, Kyung-Un Choi, Dong-Soo Suh, Byoung Soo Kim, Sanghwa Jeong, Jae Ho Kim
BMB Reports.2024; 57(12): 527. CrossRef
CD109 Promotes Drug Resistance in A2780 Ovarian Cancer Cells by Regulating the STAT3-NOTCH1 Signaling Axis
Jun Se Kim, Min Joo Shin, Seo Yul Lee, Dae Kyoung Kim, Kyung-Un Choi, Dong-Soo Suh, Dayea Kim, Jae Ho Kim
International Journal of Molecular Sciences.2023; 24(12): 10306. CrossRef
CD109 facilitates progression and 5-fluorouracil resistance of nasopharyngeal carcinoma
Zhenwei Zhu, Fang Zhou, Cheng Mao
Materials Express.2022; 12(9): 1189. CrossRef
Usefulness of CD109 expression as a prognostic biomarker in patients with cancer
Hyun Min Koh, Hyun Ju Lee, Dong Chul Kim
Medicine.2021; 100(11): e25006. CrossRef
Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma
Sumitaka Hagiwara, Eiichi Sasaki, Yasuhisa Hasegawa, Hidenori Suzuki, Daisuke Nishikawa, Shintaro Beppu, Hoshino Terada, Michi Sawabe, Masahide Takahashi, Nobuhiro Hanai
Cancer Medicine.2021; 10(4): 1335. CrossRef

The Role of TWIST in Ovarian Epithelial Cancers: Kyungbin Kim, Eun Young Park, Man Soo Yoon, Dong Soo Suh, Ki Hyung Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Mee Young Sol, Kyung Un Choi; Korean J Pathol. 2014;48(4):283-291. Published online August 26, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.4.283

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Abstract PDF

Background

Epithelial-mesenchymal transition (EMT) is associated with tumor hypoxia. EMT is regulated, in part, by the action of TWIST, which inhibits of E-cadherin expression and may interfere with the p53 tumor-suppressor pathway.

Methods

We examined the expression of TWIST, E-cadherin, hypoxia-inducible factor 1α (HIF1α), and p53 by immunohistochemistry in 123 cases of ovarian epithelial cancers (OEC) to evaluate the role of TWIST in OEC. We assessed the association between protein expression and clinicopathologic parameters.

Results

The expression of TWIST, E-cadherin, HIF1α, and p53 proteins was found in 28.5%, 51.2%, 35.0%, and 29.3% of cases, respectively. TWIST expression was associated with higher histologic grade and unfavorable survival. TWIST expression was correlated with HIF1α expression and reduced E-cadherin expression. The altered HIF1α/TWIST/E-cadherin pathway was associated with lower overall survival (OS), while the co-expression of TWIST and p53 was correlated with lower progression-free survival. In the multivariate analyses, TWIST expression was an independent prognostic factor for OS.

Conclusions

Our data imply that TWIST expression could be a useful predictor of unfavorable prognosis for OEC. TWIST may affect the p53 tumor-suppressor pathway. Moreover, hypoxia-mediated EMT, which involves the HIF1α/TWIST/E-cadherin pathway may play an important role in the progression of OEC.

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The Mechanism and Dynamic Regulation of Epithelial to Mesenchymal Transition in Ovarian Cancer
Pande Kadek Aditya Prayudi, I Gde Sastra Winata, I Nyoman Bayu Mahendra, I Nyoman Gede Budiana, Kade Yudi Saspriyana, Ketut Suwiyoga
Clinical and Experimental Obstetrics & Gynecology.2023;[Epub] CrossRef
E-Cadherin Expression in Relation to Clinicopathological Parameters and Survival of Patients with Epithelial Ovarian Cancer
Michal Kielbik, Izabela Szulc-Kielbik, Magdalena Klink
International Journal of Molecular Sciences.2022; 23(22): 14383. CrossRef
Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer
Danchen Wu, Asish Dasgupta, Austin D. Read, Rachel E.T. Bentley, Mehras Motamed, Kuang-Hueih Chen, Ruaa Al-Qazazi, Jeffrey D. Mewburn, Kimberly J. Dunham-Snary, Elahe Alizadeh, Lian Tian, Stephen L. Archer
Free Radical Biology and Medicine.2021; 170: 150. CrossRef
Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond
Shing Yau Tam, Vincent W. C. Wu, Helen K. W. Law
Frontiers in Oncology.2020;[Epub] CrossRef
Expression of selected epithelial–mesenchymal transition transcription factors in serous borderline ovarian tumors and type I ovarian cancers
Pawel Sadlecki, Jakub Jóźwicki, Paulina Antosik, Marek Grabiec
Tumor Biology.2018; 40(6): 101042831878480. CrossRef
Expression and prognostic significance of epithelial-mesenchymal transition-related markers and phenotype in serous ovarian cancer
In Hye Song, Kyu-Rae Kim, Sehun Lim, Seok-Hyung Kim, Chang Ohk Sung
Pathology - Research and Practice.2018; 214(10): 1564. CrossRef
Transcription factors controlling E-cadherin down-regulation in ovarian cancer
Holly Russell, Md Zahidul Islam Pranjol
Bioscience Horizons: The International Journal of Student Research.2018;[Epub] CrossRef
Immunohistochemical expression of TWIST in oral squamous cell carcinoma and its correlation with clinicopathologic factors
Maryam Seyedmajidi, Safoura Seifi, Dariush Moslemi, Seyyedeh-Fatemeh Mozaffari, Hemmat Gholinia, Zahra Zolfaghari
Journal of Cancer Research and Therapeutics.2018; 14(5): 964. CrossRef
Activation of TWIST1 by COL11A1 promotes chemoresistance and inhibits apoptosis in ovarian cancer cells by modulating NF‐κB‐mediated IKKβ expression
Yi‐Hui Wu, Yu‐Fang Huang, Tzu‐Hao Chang, Cheng‐Yang Chou
International Journal of Cancer.2017; 141(11): 2305. CrossRef
MicroRNA-219-5p inhibits the proliferation, migration, and invasion of epithelial ovarian cancer cells by targeting the Twist/Wnt/β-catenin signaling pathway
Chunyan Wei, Xi Zhang, Sai He, Bianli Liu, Hongfang Han, Xuejun Sun
Gene.2017; 637: 25. CrossRef
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Zi Chen, Dongwen Xu, Tao Zhang
International Journal of Oncology.2017; 51(3): 851. CrossRef
Is overexpression of TWIST, a transcriptional factor, a prognostic biomarker of head and neck carcinoma? Evidence from fifteen studies
Xianlu Zhuo, Huanli Luo, Aoshuang Chang, Dairong Li, Houyu Zhao, Qi Zhou
Scientific Reports.2015;[Epub] CrossRef

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers: Kyungbin Kim, Won Young Park, Jee Yeon Kim, Mee Young Sol, Dong Hun Shin, Do Youn Park, Chang Hun Lee, Jeong Hee Lee, Kyung Un Choi; Korean J Pathol. 2012;46(6):532-540. Published online December 26, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.6.532

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Abstract PDF

Background

Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis.

Methods

Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC).

Results

CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers.

Conclusions

The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

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Glucose-transporter 1 (GLUT1) as a prognostic biomarker: evidence from 14,966 human tumors across 134 cancer types
Seyma Büyücek, Katharina Möller, Florian Viehweger, Ria Schlichter, Anne Menz, Andreas M Luebke, Viktor Reiswich, Martina Kluth, Claudia Hube-Magg, Andrea Hinsch, Florian Lutz, Sören Weidemann, Frank Jacobsen, Maximilian Lennartz, David Dum, Christian Ber
BMC Cancer.2026;[Epub] CrossRef
Evaluation of the effect of Endogenous and Exogenous Antioxidants on Hypoxia Induced Breast Adenocarcinoma Cell Invasion and Migration: In vitro
Subarnarekha Maitra, Poulami Sen, Dibya Sinha, Tathagata Roy
Research Journal of Pharmacy and Technology.2025; : 3153. CrossRef
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Shinwoo Kang, Dongho Keum
Journal of Korean Medicine Rehabilitation.2023; 33(4): 167. CrossRef
A systematic review verified by bioinformatic analysis based on TCGA reveals week prognosis power of CAIX in renal cancer
Zikuan Zhang, Bo Wu, Yuan Shao, Yongquan Chen, Dongwen Wang, Lucia Magnelli
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Sunjoo An, Dongho Keum
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Abeer F. Mostafa, Shereen M. Samir, R.M. Nagib
Canadian Journal of Physiology and Pharmacology.2018; 96(4): 395. CrossRef
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Jennifer X Ji, Yi Kan Wang, Dawn R Cochrane, David G Huntsman
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Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis
Simon J. A. van Kuijk, Ala Yaromina, Ruud Houben, Raymon Niemans, Philippe Lambin, Ludwig J. Dubois
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Review of Research Topics on Abdominal Examination
Jihye Kim, Jeong Hwan Park, Keun Ho Kim
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Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma
JEUNG IL KIM, KYUNG UN CHOI, IN SOOK LEE, YOUNG JIN CHOI, WON TACK KIM, DONG HOON SHIN, KYUNGBIN KIM, JEONG HEE LEE, JEE YEON KIM, MEE YOUNG SOL
Oncology Letters.2015; 9(4): 1699. CrossRef
Evaluation of a Hypoxia Regulated Gene Panel in Ovarian Cancer
Amanda F. Baker, Scott W. Malm, Ritu Pandey, Cindy Laughren, Haiyan Cui, Denise Roe, Setsuko K. Chambers
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Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy
MICHAL PASTOREK, VERONIKA SIMKO, MARTINA TAKACOVA, MONIKA BARATHOVA, MARIA BARTOSOVA, LUBA HUNAKOVA, OLGA SEDLAKOVA, SONA HUDECOVA, OLGA KRIZANOVA, FRANCK DEQUIEDT, SILVIA PASTOREKOVA, JAN SEDLAK
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Overexpression of Glucose Transporter-1 (GLUT-1) Predicts Poor Prognosis in Epithelial Ovarian Cancer
Hanbyoul Cho, You Sun Lee, Julie Kim, Joon-Yong Chung, Jae-Hoon Kim
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Jonathan Cimino, David Calligaris, Johann Far, Delphine Debois, Silvia Blacher, Nor Sounni, Agnès Noel, Edwin De Pauw
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Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression.: Nari Shin, Hye Yeon Kim, Woo Kyung Kim, Min Gyung Park, Kyung Bin Kim, Dong Hoon Shin, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Gi Young Huh, Mee Young Sol, Do Youn Park; Korean J Pathol. 2011;45(1):69-78.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.69

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Abstract PDF

BACKGROUND
It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer.
METHODS
We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH).
RESULTS
Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes.
CONCLUSIONS
Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.

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Mucin Expression in Gastric Cancer: Reappraisal of Its Clinicopathologic and Prognostic Significance
Dae Hwan Kim, Nari Shin, Gwang Ha Kim, Geum Am Song, Tae-Yong Jeon, Dong-Heon Kim, Gregory Y. Lauwers, Do Youn Park
Archives of Pathology & Laboratory Medicine.2013; 137(8): 1047. CrossRef
Microsatellite Instability Status in Gastric Cancer: A Reappraisal of Its Clinical Significance and Relationship with Mucin Phenotypes
Joo-Yeun Kim, Na Ri Shin, Ahrong Kim, Hyun-Jeong Lee, Won-young Park, Jee-Yeon Kim, Chang-Hun Lee, Gi-Young Huh, Do Youn Park
Korean Journal of Pathology.2013; 47(1): 28. CrossRef

Analysis of Microsatellite Instability in Ovarian Epithelial Cancer.: Mee Young Sol, Kyung Un Choi, Jee Yeon Kim, Hyun Jeong Kang, Dong Hoon Shin, Ik Doo Kim, Hyo Seon Choi, Soon Jung Seo; Korean J Pathol. 2007;41(6):380-386.

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Abstract PDF: BACKGROUND
The aim of this study was to clarify the incidence and role of microsatellite instability (MSI) in sporadic ovarian epithelial cancers (OEC). We investigated the MSI status and mismatch repair (MMR) protein expression in OEC.
METHODS
MSI was examined by fluorescence- based polymerase chain reaction using five NCI panel markers (BAT25, BAT26, D2S123, D5S346 and D17S250) in 46 cases of OEC. Immunohistochemistry (IHC) for hMLH1 and hMSH2 was performed.
RESULTS
Seven cases (15.2%) exhibited high-frequency MSI (MSIH), one exhibited low-frequency MSI (MSI-L), and the remaining 38 demonstrated microsatellite stability (MSS). MSI-H in OEC was not associated with histologic grade, FIGO stage, tumor size, mitoses or histologic type. Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 7 (59.3%) MSI-H cases, whereas 4 of the 39 (10.3%) MSI-L or MSS tumors revealed loss of expression of MMR proteins. The sensitivity and specificity of immunohistochemistry for hMLH1 and hMSH2 were 57.1% and 89.7%.
CONCLUSIONS
Our data suggest that a genetic defect in the MMR system might play a role in the carcinogenesis of a minor subset of sporadic OEC however, immunohistochemical testing for hMLH1 and hMSH2 cannot accurately determine microsatellite instability status in OEC.

Expression of Fas/Fas Ligand and Its Relationship with Apoptosis in Chemically Induced Preneoplastic Lesions in Rat Liver.: Hye Jin Lee, Do Youn Park, Kyung Un Choi, Jee Yeon Kim, Chang Hun Lee, Mee Young Sol, Kang Suek Suh; Korean J Pathol. 2001;35(5):383-390.

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Abstract PDF: BACKGROUND
Apoptosis of hepatocytes plays a major role in experimental hepatocarcinogenesis of rats. But sequential change and localization of Fas and Fas ligand (FasL) in preneoplastic lesions and the relationship with apoptosis are not clearly elucidated.
METHODS
We investigated sequential change and localization of Fas/FasL and its relationship to apoptosis in preneoplastic lesions of chemical hepatocarcinogenesis in rats using northern blot analysis, immunohistochemistry and terminal deoxynucleotidyl transferase end labeling (TUNEL) assay.
RESULTS
We found that mRNA of Fas and Fas ligand increased for up to 42 days and 14 days after partial hepatectomy, respectively, and thereafter decreased with time. Fas protein was localized on the cytoplasm of hepatocytes of preneoplastic lesions, as well as on the cytoplasmic membrane of the adjacent liver parenchyme. Fas negative preneoplastic lesions were evident at 42 days after partial hepatectomy. FasL protein was found only in the cytoplasm of hepatocytes of preneoplastic lesions, instead of in the adjacent liver parenchyme. FasL-positive hepatocytes increased with time for up to 14 days after partial hepatectomy and therafter decreased. Also, TUNEL-positive apoptotic cells increased with time and were more numerous in the adjacent liver parenchyme than in the preneoplastic lesions.
CONCLUSIONS
It was suggested that Fas/FasL-mediated apoptosis might be one of the major mechanisms for controlling apoptotic cell death in the promotion stage of chemical hepatocarcinogenesis.

Immunohistochemical Study of E-cadherin Expression in Gastric Adenocarcinomas.: Jee Yeon Kim, Mee Young Sol, Sun Kyung Lee; Korean J Pathol. 1997;31(8):745-753.

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Abstract PDF: E-cadherin (ECD) is a Ca++ -dependent adhesion molecule which plays a major role in the maintenance of intercellular adhesion in epithelial tissues. The expression pattern of ECD in 77 surgically resected gastric adenocarcinomas was examined by immunohistochemistry, using a rat monoclonal antibody raised against murine E-cadherin (DECAM-1). ECD was strongly expressed uniformly at cell to cell borders in normal gastric epithelium without exception. But, various staining patterns were observed in the cancer tissues. The frequency of tumors with preserved ECD expression (Pre-type) and reduced ECD expression (Rd-type) was 44% and 56%, respectively. Using Lauren's classification, the high frequency of the Pre-type expression in adenocarcinoma of the intestinal type was significantly higher than that in adenocarcinoma of the diffuse type (p<0.05). But, no significant correlation between the ECD expression and the gross type, invasion depth, growth pattern or metastasis was observed. These results suggest that ECD might play a key role in the morphogenesis of gastric adenocarcinoma.

Case Reports

Cytologic Features of Fine Needle Aspirates of Hyalinizing Trabecular Adenoma with Occult Papillary Carcinoma of the Thyroid.: Kyung Un Choi, Jee Yeon Kim, Jin Sook Lee, Do Youn Park, Chang Hoon Lee, Mee Young So, Kang Suek Suh; J Pathol Transl Med. 2003;14(1):7-11.

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Abstract PDF: Hyalinizing trabecular adenoma of the thyroid gland is a rare benign neoplasm predominantly diagnosed in middle-aged women. Carney et al. first described this entity that may mimic paraganglioma, medullary carcinoma and papillary carcinoma in 1987. We describe cytologic and histopathologic features of a case of hyalinizing trabecular adenoma combined with occult papillary carcinoma in the opposite lobe. A 55-year-old woman presented with nontender palpable mass of the right neck for 6 months. The aspirate was cellular and contained small clusters and sheets of epithelial cells with abundant filamentous, vacuolated, and ill-defined cytoplasm. The nuclei were slightly pleomorphic and showed nuclear overlapping, nuclear grooves, and intranuclear cytoplasmic inclusions. Histologic examination showed hyalinizing trabecular adenoma in the right lobe and occult papillary carcinoma in the left lobe.

Fine Needle Aspiration Cytology of Insular Carcinoma of the Thyroid.: Kyung Un Choi, Jee Yeon Kim, Jin Sook Lee, Chang Hun Lee; J Pathol Transl Med. 2003;14(1):17-21.

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Abstract PDF: Insular carcinoma of the thyroid(ICT) is an uncommon thyroglobulin-producing neoplasm, intermediate between well differentiated and anaplastic carcinoma. Only a few publications have addressed the fine needle aspiration cytologic(FNAC) findings from ICT. We experienced a case histologically diagnosed as ICT and with preoperative FNAC in a 52-year-old woman. The FNAC displayed scanty colloid and abundant monomorphic follicular cells presented singly, in small loose aggregates, and in cohesive trabecular or acinar clusters. Intact insulae of tumor cells were also identified. Necrosis and mitosis were rare. Tumor cells showed round and monomorphic nuclei, finely granular chromatin, and inconspicuous nucleoli. When insular structure is identified in thyroid FNAC specimen, ICT should be included in the differential diagnosis. Herein we discuss and review the cytologic criteria for separation of ICT from other thyroid neoplasms.

Original Articles

Primary MALT(mucosa-associated lymphoid tissue) Type Lymphoma of the Liver.: Do Youn Park, Jee Yeon Kim, Hyo Jeong Chae, Jin Sook Lee, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1997;31(12):1317-1319.

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Abstract PDF: Primary non-Hodgkin' lymphomas of the liver, an organ normally devoid of a native lymphoid tissue, are very rare. We recently experienced a case of a primary low-grade hepatic B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type in a 36-year-old woman. The ultrasonography revealed a 5 cm sized mass in the right lobe of the liver. A right segmentectomy of the liver was done and showed a relatively well-circumscribed brownish yellow lobulated homogenous mass, measuring 5.5x4.5 cm in size. Histologic sections of liver mass revealed large lymphoid follicles with reactive germinal centers, follicular colonization by centrocyte-like cells (CCL cells), and lymphoepithelial lesions. The CCL cells were positive for B-cell (CD20), LCA (CD45RA), Bcl-2 oncoprotein, and lambda light chain.

Altered Expression of DNA Topoisomerase IIalpha, Ki-67, p53 and p27 in Non-Hodgkin's Lymphoma.: Kyeong Min Lee, Mee Young Sol, Hyun Jeong Kang, Dong Hoon Shin, Kyung Un Choi, Hwal Woong Kim, Jee Yeon Kim, Do Youn Park, Chang Hun Lee; Korean J Pathol. 2005;39(5):332-337.

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Abstract PDF: BACKGROUND
Topoisomerase II (TOPO II) is an enzyme that separates intertwined chromosomes during DNA synthesis by transiently breaking and joining DNA strands. The level of TOP II is one of the determinants of cellular sensitivity to anti-tumor drugs in non-Hodgkin's lymphoma patients. The alpha form of TOPO II has been recently used as a marker of cellular proliferation. High levels of TOPO IIalpha are expressed in aggressive and proliferative tumors.
METHODS
This study was designed to evaluate the relationship between TOPO IIalpha expression and clinicopathological parameters including age, gender, the serum LDH level, the serum beta2-microglobulin level and stage, or expressions, of Ki-67, p53 and p27, in non-Hodgkin's lymphoma. We analyzed forty-one biopsied tissue specimens from patients with non-Hodgkin's lymphoma.
RESULTS
The expression of TOPO IIalpha increased with the clinical stage and it was correlated with Ki-67 and p53 expressions. However, TOPO IIalpha expression did not have any significant correlation with age, gender, the serum LDH level, the serum 2-microglobulin level and the p27 expression.
CONCLUSIONS
TOPO IIalpha expression is a useful marker of cellular proliferation and it may serve as a prognostic factor of a tumor's progression and aggressiveness in non-Hodgkin's lymphomas.

Case Reports

Cytologic Features of Pseudoangiomatous Stromal Hyperplasia of the Breast: A Case Report with Review of Literature.: Jin Sook Lee, Jee Yeon Kim, Dong Hoon Shin, Do Youn Park, Kyung Un Choi, Chang Hoon Lee, Mee Young Sol; J Pathol Transl Med. 2005;16(1):25-30.

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Abstract PDF: Pseudoangiomatous stromal hyperplasia(PASH) was initially described by Vuitch et al. as a benign breast lesion, consisting of mammary stromal proliferations which simulate vascular lesions, and which might be mistaken for a low-grade angiosarcoma. This condition occasionally presents as a palpable mass in postmenopausal women, but is more frequently encountered as an incidental component in premenopausal women. Clinical, radiological, and fine-needle aspiration(FNA) findings associated with this condition can mimic those observed in conjunction with a phyllodes tumor or a fibroadenoma. The cytological features of PASH are generally nonspecific, and its diagnosis by FNA cytology is fairly difficult. In this study, we report a case of PASH, manifesting as a palpable mass

Invasine Ductal Carcinoma with Osteoclast-Like Giant Cell in a Young Woman.: Hyun Jeong Kang, Jee Yeon Kim, Kyung Un Choi, Hee Suk Kwak, Mee Young Sol; J Pathol Transl Med. 2007;18(1):69-73.

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Abstract PDF: Mammary carcinoma with osteoclast-like giant cells is an unusual neoplasm characterized by giant cells, mononuclear stromal cells, and hemorrhage accompanying a low grade carcinoma. We present the cytological findings in a case of invasive ductal carcinoma with osteoclast-like giant cells that was initially confused with a fibroadenoma, due to its well-demarcated and soft mass and the young age of the patient. A 28-year-old female presented with a 4.5 cm, well demarcated, soft and nontender mass in the right breast. Fine needle aspiration cytology (FNAC) showed a combination of low grade malignant epithelial cell clusters and osteoclast-like giant cells. The atypical epithelial cells were present in cohesive sheets and clusters. Osteoclast-like giant cells and bland-looking mononuclear cells were scattered. An histological examination revealed the presence of an invasive ductal carcinoma with osteoclast-like giant cells. We report here the cytological findings of this rare carcinoma in a very young woman. The minimal atypia of the epithelial cells and its soft consistency may lead to a false negative diagnosis in a young woman. The recognition that osteoclastlike giant cells are rarely present in a low grade carcinoma, but not in benign lesion, can assist the physician in making a correct diagnosis.

Review

General Cytological Characters of Malignant Breast Lesions.: Jee Yeon Kim; J Pathol Transl Med. 2007;18(2):100-111.

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Abstract PDF: Fine needle aspiration (FNA) cytology of breast disease is recognized to be highly accurate and cost effective, especially when this is used in combination with clinical examination and imaging as part of a triple approach. A probabilistic/categorical approach is used for the classification of breast FNA specimens. Criteria are defined from the perspective of the likelihood of making a definitive diagnosis of cancer on excision. This approach is an accurate way of classifying breast FNA specimens, and this can be reliably applied regardless of the level of experience of the pathologist for interpreting the case. When a definitive diagnosis of malignancy is made, the next step is to determining the specific histologic types of the malignancy according to their cytological features. In order to make an accurate diagnosis of carcinoma and for correct typing a tumor, an adequate, correctly sampled aspirate without any other artifacts is required.

Original Articles

Fine Needle Aspiration Cytology of Palpable Lymph Nodes: A Single Institutional Experience of 1,346 Cases.: Dong Hoon Shin, Kyung Un Choi, Jee Yeon Kim, Hyun Jeong Kang, Ick Doo Kim, Mee Young Sol; J Pathol Transl Med. 2007;18(2):126-132.

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Abstract PDF: The aim of this study was to evaluate the diagnostic value of fine needle aspiration cytology (FNAC) for the assessment of palpable enlarged lymph nodes. The authors reviewed the results of 1,346 FNACs of palpable enlarged lymph nodes performed at Pusan National University Hospital from 1998 to 2004. Of the 1,346 cases, 1,265 (94.0%) were satisfactory and 81 (6.0%) unsatisfactory. Cytologic diagnoses were judged in 488 cases, based on subsequent histologic diagnoses, clinical follow up, or both. Global results for all malignancies (lymphoid and non-lymphoid neoplasms) based on cases with final diagnoses, showed a sensitivity of 87.4% and a specificity of 98.7%. The overall diagnostic accuracy was 93.2%, and the false negative rate reduced from 12.6% to 7.3% when lymphomatous cases were excluded. The annual data for this period showed that the number of diagnostic lymph node biopsies and the rate of inadequately sampled material markedly decreased. Gene rearrangement studies for IgH and TCR gamma were helful in 30 cases. FNAC is a useful initial diagnostic procedure for the evaluation of palpable enlarged lymph nodes. However, the technique should be assisted by the appropriate ancillary studies and by proper interpretation by a cytopathologist.

Alteration of G1/S Cell Cycle Regulatory Proteins in Ovarian Epithelial Tumors.: Jee Yeon Kim, Hwal Woong Kim, Kyung Un Choi, Chang Hun Lee, Mee Young Sol, Hyun Jeong Kang, Dong Hoon Shin; Korean J Pathol. 2006;40(4):274-281.

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Abstract PDF: BACKGROUND
Disturbances of the cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study was to evaluate the expression of G1/S cell cycle regulatory proteins in ovarian epithelial tumor.
METHODS
We simultaneously evaluated the expression of cyclin D1, cyclin E, CDK4, CDK2, p16, Rb, E2F1, p53 and the Ki67 labelling index (LI) by immunohistochemical methods in 148 cases of ovarian epithelial tumor of the benign (n=47), borderline (n=29), and malignant type (n=72).
RESULTS
The expression of cyclin E, CDK2, p16, Rb, E2F1, p53 and the Ki67 LI gradually increased from the benign type, through the borderline type, to the malignant tumors. Between the borderline and malignant tumors, the increased expression of cyclin E, E2F1, and p53, and the decreased expression of Rb were significantly associated with malignancy. The reduced Rb expression and the increased E2F1 expression were correlated with the FIGO stage and the histologic grade in the malignant ovarian epithelial tumors. CONCLUSIONS: Cyclin E, E2F1, and p53 overexpressions and the loss of Rb are the important components during carcinogenesis of ovarian epithelial tumors. Our results suggest that in- creased expression of E2F1 should be considered as a new parameter for the prognosis of patients with malignant ovarian epithelial tumors.

Overexpression of Insulin-like Growth Factor Binding Protein 3 in Colorectal Carcinoma Identified by cDNA Microarray and Immunohistochemical Analysis.: Kyung Un Choi, Do Youn Park, Jee Yeon Kim, Jin Sook Lee, Mee Young Sol; Korean J Pathol. 2003;37(3):166-173.

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Abstract PDF: BACKGROUND
Insulin-like growth factor binding protein 3 (IGFBP3), a member of six proteins with a high affinity for insulin-like growth factors (IGFs), seems to modulate the effects of IGFs on cells and to regulate cell proliferation through the IGF-independent pathway. We assessed the role of IGFBP3 in the colorectal carcinoma detected by cDNA microarray.
METHODS
To identify molecular alterations in the colorectal carcinoma, we analyzed gene expression profiles of the colorectal adenocarcinoma by means of a cDNA microarray representing 7,500 genes. Of the differentially expressed genes, the author assessed the insulin-like growth factor binding protein 3 (IGFBP3) gene at the protein level using immunohistochemistry.
RESULTS
The expressions of 21 and 16 genes were noted to have more than fivefold increases or decreases in the colonic adenocarcinoma tissue compared with the noncancerous colonic mucosal tissue. The differentially expressed genes include those associated with cell proliferation/apoptosis, signal transduction/transcription, metabolizing enzymes, cytoskeleton, angiogenesis, ion channel, extracellular matrix and others. Of the total 68 cases of colorectal adenocarcinomas observed, 34 cases (50%) showed positive immunohistochemical stainings for IGFBP3.
CONCLUSIONS
In this study, it is suggested that IGFBP3 plays a role in colorectal carcinogenesis. And combining an immunohistochemistry with a cDNA microarray can facillitate the rapid characterization of a candidate novel molecular target.

Assessment of Apoptosis by M30 Immunoreactivity and the Relationship with the MSI status and the Clinicopathological Characteristics of Colorectal Carcinomas.: Hyun Jeong Kang, Mee Young Sol, Do Youn Park, Soo Han Lee, Dong Hun Shin, Jee Yeon Kim, Kyung Un Choi, Hwal Woong Kim, Chang Hun Lee, Gi Young Huh; Korean J Pathol. 2006;40(5):319-325.

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Abstract PDF: BACKGROUND
The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 that's produced during the process of apoptosis, and it is reactive in formalin-fixed, paraffin-embedded tissue. The detailed nature of apoptosis in colorectal cancer is unclear, especially in regard to the MSI status and the clinicopathologic factors. The purpose of this study was to elucidate the apoptosis assessed by M30 immunoreactivity in colorectal cancer and its relationship with the MSI status and the various clinicopathologic factors of colorectal cancers.
METHODS
101 colorectal cancers were classified according to levels of MSI as 12 MSI-H, 4 MSI-L and 85 MSS. Apoptosis was quantified by immunohistochemistry with using M30 CytoDEATH anti-body.
RESULTS
The apoptotic index assessed by M30 was significantly increased in the MSI-H and MSI-L colorectal cancer compared to that in the MSS colorectal cancer. Right sided colon cancer showed a significant higher apoptotic index than did the left sided colon cancer. There was also a tendency for decreased apoptosis in metastatic colorectal cancers (Duke's stage D). There was somewhat of an increase of apoptosis in colorectal cancers with mucinous carcinoma and medullary carcinoma, and also in the colorectal cancers with an increased TIL count, but this was not statistically significant.
CONCLUSION
M30 immunoreactivity is a valuable method to detect apoptosis in formalin-fixed, paraffin-embedded tissue and it might explain that MSI-H colorectal cancer shows better clinical behavior than MSS colorectal cancer in regard to the increased apoptosis.

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