Journal of Pathology and Translational Medicine

Geon Kook Lee

9 Articles

Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea: Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha; J Pathol Transl Med. 2022;56(6):334-341. Published online October 27, 2022; DOI: https://doi.org/10.4132/jptm.2022.08.22

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Background
Next-generation sequencing (NGS) is an approved test to select patients for BRAF V600E targeted therapy in Korea. However, the high cost, long turnaround times, and the need for sophisticated equipment and skilled personnel limit the use of NGS in daily practice. Immunohistochemistry (IHC) is a rapid and relatively inexpensive assay available in most laboratories. Therefore, in this study, we evaluate the usefulness of BRAF VE1 IHC in terms of predictive value and interobserver agreement in non–small cell lung cancers (NSCLCs).
Methods
A total of 30 cases with known BRAF mutation status were selected, including 20 cases of lung adenocarcinomas, six cases of colorectal adenocarcinomas, and four cases of papillary thyroid carcinomas. IHC for BRAF V600E was carried out using the VE1 antibody. Fifteen pathologists independently scored both the staining intensity and the percentage of tumor cell staining on whole slide images.
Results
In the lung adenocarcinoma subset, interobserver agreement for the percentage of tumor cell staining and staining intensity was good (percentage of tumor cell staining, intraclass correlation coefficient = 0.869; staining intensity, kappa = 0.849). The interobserver agreement for the interpretation using the cutoff of 40% was almost perfect in the entire study group and the lung adenocarcinoma subset (kappa = 0.815). Sensitivity, specificity, positive predictive value, and negative predictive value of BRAF VE1 IHC were 80.0%, 90.0%, 88.9%, and 81.8%, respectively.
Conclusions
BRAF VE1 IHC could be a screening test for the detection of BRAF V600E mutation in NSCLC. However, further studies are needed to optimize the protocol and to establish and validate interpretation criteria for BRAF VE1 IHC.

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef
Differentiating BRAF V600E- and RAS-like alterations in encapsulated follicular patterned tumors through histologic features: a validation study
Chankyung Kim, Shipra Agarwal, Andrey Bychkov, Jen-Fan Hang, Agnes Stephanie Harahap, Mitsuyoshi Hirokawa, Kennichi Kakudo, Somboon Keelawat, Chih-Yi Liu, Zhiyan Liu, Truong Phan-Xuan Nguyen, Chanchal Rana, Huy Gia Vuong, Yun Zhu, Chan Kwon Jung
Virchows Archiv.2024; 484(4): 645. CrossRef
BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients
Hyo Yeong Ahn, Chang Hun Lee, Min Ki Lee, Jung Seop Eom, Yeon Joo Jeong, Yeong Dae Kim, Jeong Su Cho, Jonggeun Lee, So Jeong Lee, Dong Hoon Shin, Ahrong Kim
Medicina.2023; 59(6): 1085. CrossRef
Reevaluating diagnostic categories and associated malignancy risks in thyroid core needle biopsy
Chan Kwon Jung
Journal of Pathology and Translational Medicine.2023; 57(4): 208. CrossRef

Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group: Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee; J Pathol Transl Med. 2021;55(3):181-191. Published online May 11, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.23

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Abstract PDF

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

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Discovery of mutations predictive of survival benefit from immunotherapy in first-line NSCLC: A retrospective machine learning study of IMpower150 liquid biopsy data
Min Yuan, Wei Feng, Haolun Ding, Yaning Yang, Xu Steven Xu
Computers in Biology and Medicine.2025; 189: 109964. CrossRef
Clinical utility of the Oncomine Dx Target Testmulti‐CDxsystem and the possibility of utilizing those original sequence data
Ayaka Saito, Hideki Terai, Tae‐Jung Kim, Katsura Emoto, Ryutaro Kawano, Kohei Nakamura, Hideyuki Hayashi, Hatsuyo Takaoka, Akihiko Ogata, Katsuhito Kinoshita, Fumimaro Ito, Lisa Shigematsu, Masahiko Okada, Takahiro Fukushima, Akifumi Mitsuishi, Taro Shino
Cancer Medicine.2024;[Epub] CrossRef
Clinicopathologic and Molecular Characteristics of HER2 (ERBB2)-Altered Non–Small Cell Lung Cancer: Implications for Precision Medicine
Yurimi Lee, Boram Lee, Yoon-La Choi, Dong-Wook Kang, Joungho Han
Modern Pathology.2024; 37(6): 100490. CrossRef
Pleural effusion supernatant: a reliable resource for cell-free DNA in molecular testing of lung cancer
Shilpi Thakur, Amber Rathor, Surabhi Jain, Aruna Nambirajan, Sachin Khurana, Prabhat Singh Malik, Deepali Jain
Journal of the American Society of Cytopathology.2024; 13(4): 291. CrossRef
A Novel Dual-labeled Peptide for Multimodal Imaging of EGFR with L858R Mutation
Myoung Hyoun Kim, Seul-Gi Kim, Dae-Weung Kim
Current Radiopharmaceuticals.2024; 17(2): 174. CrossRef
The Advantage of Targeted Next-Generation Sequencing over qPCR in Testing for Druggable EGFR Variants in Non-Small-Cell Lung Cancer
Adam Szpechcinski, Joanna Moes-Sosnowska, Paulina Skronska, Urszula Lechowicz, Magdalena Pelc, Malgorzata Szolkowska, Piotr Rudzinski, Emil Wojda, Krystyna Maszkowska-Kopij, Renata Langfort, Tadeusz Orlowski, Pawel Sliwinski, Mateusz Polaczek, Joanna Chor
International Journal of Molecular Sciences.2024; 25(14): 7908. CrossRef
Cost-effectiveness of next-generation sequencing for advanced EGFR/ALK-negative non-small cell lung cancer
Dong-Won Kang, Sun-Kyeong Park, Sokbom Kang, Eui-Kyung Lee
Lung Cancer.2024; 197: 107970. CrossRef
FACILITATE: A real-world, multicenter, prospective study investigating the utility of a rapid, fully automated real-time PCR assay versus local reference methods for detecting epidermal growth factor receptor variants in NSCLC
Anke Behnke, Anne Cayre, Giovanna De Maglio, Giuseppe Giannini, Lionel Habran, Marina Tarsitano, Massimiliano Chetta, David Cappellen, Alexandra Lespagnol, Cecile Le Naoures, Gabriella Massazza, Annarita Destro, Irina Bonzheim, Achim Rau, Achim Battmann,
Pathology and Oncology Research.2023;[Epub] CrossRef
Problems in the Pathologic Diagnosis of Suspected Lung Cancer
Soo Han Kim, Mi-Hyun Kim, Min Ki Lee, Jung Seop Eom
Tuberculosis and Respiratory Diseases.2023; 86(3): 176. CrossRef
Mesonephric-like Adenocarcinoma of the Ovary: Clinicopathological and Molecular Characteristics
Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
Diagnostics.2022; 12(2): 326. CrossRef
Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(5): 1102. CrossRef
Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2022; 56(5): 249. CrossRef
Biomarker testing of cytology specimens in personalized medicine for lung cancer patients
Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2022; 56(6): 326. CrossRef
Usefulness of BRAF VE1 immunohistochemistry in non–small cell lung cancers: a multi-institutional study by 15 pathologists in Korea
Sunhee Chang, Yoon-La Choi, Hyo Sup Shim, Geon Kook Lee, Seung Yeon Ha
Journal of Pathology and Translational Medicine.2022; 56(6): 334. CrossRef
Lung Cancer in Korea
Sehhoon Park, Chang-Min Choi, Seung-Sik Hwang, Yoon-La Choi, Hyae Young Kim, Young-Chul Kim, Young Tae Kim, Ho Yun Lee, Si Yeol Song, Myung-Ju Ahn
Journal of Thoracic Oncology.2021; 16(12): 1988. CrossRef

Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group: Dong Hoon Shin, Hyo Sup Shim, Tae Jung Kim, Heae Surng Park, Yun La Choi, Wan Seop Kim, Lucia Kim, Sun Hee Chang, Joon Seon Song, Hyo jin Kim, Jung Ho Han, Chang Hun Lee, Geon Kook Lee, Se Jin Jang; J Pathol Transl Med. 2019;53(3):153-158. Published online February 28, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.22

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Abstract PDF

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Comparison of tissue-based and plasma-based testing for EGFR mutation in non–small cell lung cancer patients
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Exosomes in Lung Cancer: Actors and Heralds of Tumor Development
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Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
Current status and future perspectives of liquid biopsy in non-small cell lung cancer
Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim
Journal of Pathology and Translational Medicine.2020; 54(3): 204. CrossRef
Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center
Hazem Assi, Arafat Tfayli, Nada Assaf, Sarah Abou Daya, Aram H. Bidikian, Dima Kawsarani, Puzant Fermanian, Ghazi Zaatari, Rami Mahfouz
Molecular Biology Reports.2019; 46(4): 3671. CrossRef

Molecular Testing of Lung Cancers: Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee; J Pathol Transl Med. 2017;51(3):242-254. Published online April 21, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.10

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Abstract PDF

Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories—mutations, gene rearrangements, and amplifications—and propose expanded guidelines on molecular testing of lung cancers.

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Association between PD-L1 expression with EGFR, ALK, and ROS1 driver oncogene mutations in non-small cell lung cancer
Dülger Onur, Yaylım İlhan, Öz Büge
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Raquel Ramos, Conceição Souto Moura, Mariana Costa, Nuno Jorge Lamas, Renato Correia, Diogo Garcez, José Miguel Pereira, Carlos Sousa, Nuno Vale
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A. F. Nasretdinov, A. V. Sultanbaev, Sh. I. Musin, K. V. Menshikov, R. T. Ayupov, A. A. Izmailov, G. A. Serebrennikov, V. E. Askarov, D. V. Feoktistov
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Cost-effectiveness of next-generation sequencing for advanced EGFR/ALK-negative non-small cell lung cancer
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Romain Larrue, Sandy Fellah, Nihad Boukrout, Corentin De Sousa, Julie Lemaire, Carolane Leboeuf, Marine Goujon, Michael Perrais, Bernard Mari, Christelle Cauffiez, Nicolas Pottier, Cynthia Van der Hauwaert
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Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2022; 56(5): 249. CrossRef
Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
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Mercedes L Dalurzo, Alejandro Avilés-Salas, Fernando Augusto Soares, Yingyong Hou, Yuan Li, Anna Stroganova, Büge Öz, Arif Abdillah, Hui Wan, Yoon-La Choi
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Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing
Eunhyang Park, Hyo Sup Shim
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High prevalence of ROS1 gene rearrangement detected by FISH in EGFR and ALK negative lung adenocarcinoma
Yuyin Xu, Heng Chang, Lijing Wu, Xin Zhang, Ling Zhang, Jing Zhang, Yuan Li, Lei Shen, Xiaoli Zhu, Xiaoyan Zhou, Qianming Bai
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Jasna Metovic, Luisella Righi, Luisa Delsedime, Marco Volante, Mauro Papotti
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Molecular Diagnostic Assays and Clinicopathologic Implications of MET Exon 14 Skipping Mutation in Non–small-cell Lung Cancer
Eun Kyung Kim, Kyung A. Kim, Chang Young Lee, Sangwoo Kim, Sunhee Chang, Byoung Chul Cho, Hyo Sup Shim
Clinical Lung Cancer.2019; 20(1): e123. CrossRef
PD‐L1 expression in ROS1‐rearranged non‐small cell lung cancer: A study using simultaneous genotypic screening of EGFR, ALK, and ROS1
Jongmin Lee, Chan Kwon Park, Hyoung‐Kyu Yoon, Young Jo Sa, In Sook Woo, Hyo Rim Kim, Sue Youn Kim, Tae‐Jung Kim
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Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung
Journal of Pathology and Translational Medicine.2019; 53(2): 86. CrossRef
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Somatic mutations and immune checkpoint biomarkers
Brielle A. Parris, Eloise Shaw, Brendan Pang, Richie Soong, Kwun Fong, Ross A. Soo
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Genetic and clinicopathologic characteristics of lung adenocarcinoma with tumor spread through air spaces
Jae Seok Lee, Eun Kyung Kim, Moonsik Kim, Hyo Sup Shim
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Review of Medical Advisory Services by the Korean Society of Pathologists from 2003 to 2014: Min Hye Jang, Geon Kook Lee, Han Seong Kim, Wan Seop Kim; J Pathol Transl Med. 2016;50(1):37-44. Published online November 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.18

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Abstract PDF Supplementary Material: Background
Since 2003, the Korean Society of Pathologists (KSP) has been officially providing medical advisory services (MAS). We reviewed the cases submitted to the KSP between 2003 and 2014. Methods: In total, 1,950 cases were submitted, most by private health insurance companies. The main purposes of the consultations were to clarify the initial diagnoses and to assign a proper disease classification code. We comprehensively reviewed 1,803 consultation cases with detailed information. Results: In spite of some fluctuations, the number of submitted cases has been significantly increasing over the 12 study years. The colon and rectum (40.3%), urinary bladder (14.2%), and stomach (6.9%) were the three most common tissues of origin. The most common diagnoses for each of the three tissues of origin were neuroendocrine tumor (50.7%), non-invasive papillary urothelial carcinoma (70.7%), and adenocarcinoma (36.2%). Regardless of the tissue of origin, neuroendocrine tumor of the digestive system was the most common diagnosis (419 of 1,803). Conclusions: In the current study, we found that pathologic consultations associated with private health insurance accounted for a large proportion of the MAS. Coding of the biologic behavior of diseases was the main issue of the consultations. In spite of the effort of the KSP to set proper guidelines for coding and classification of tumors, this review revealed that problems still exist and will continue to be an important issue.

Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey: Sang Hwa Lee, Wan Seop Kim, Yoo Duk Choi, Jeong Wook Seo, Joung Ho Han, Mi Jin Kim, Lucia Kim, Geon Kook Lee, Chang Hun Lee, Mee Hye Oh, Gou Young Kim, Sun Hee Sung, Kyo Young Lee, Sun Hee Chang, Mee Sook Rho, Han Kyeom Kim, Soon Hee Jung, Se Jin Jang, The Cardiopulmonary Pathology Study Group of Korean Society of Pathologists; J Pathol Transl Med. 2015;49(6):481-488. Published online October 13, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.14

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Abstract PDF

Background
Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. Methods: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. Results: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. Conclusions: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.

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Guideline Recommendations for Testing of ALK Gene Rearrangement in Lung Cancer: A Proposal of the Korean Cardiopulmonary Pathology Study Group: Hyojin Kim, Hyo Sup Shim, Lucia Kim, Tae-Jung Kim, Kun Young Kwon, Geon Kook Lee, Jin-Haeng Chung; Korean J Pathol. 2014;48(1):1-9. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.1

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Abstract PDF

Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of the ALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detect ALK-rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Guideline Recommendations for EGFR Mutation Testing in Lung Cancer: Proposal of the Korean Cardiopulmonary Pathology Study Group: Hyo Sup Shim, Jin-Haeng Chung, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Geon Kook Lee, Soon-Hee Jung, Se Jin Jang; Korean J Pathol. 2013;47(2):100-106. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.100

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Abstract PDF

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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WITHDRAWN:A Clinicopathologic Study of 220 Cases of Pulmonary Sclerosing Pneumocytoma in Korea: A Nationwide Survey: Myunghee Kang, Seung Yeon Ha, Joung Ho Han, Mee Sook Roh, Se Jin Jang, Hee Jin Lee, Heae Surng Park, Geon Kook Lee, Kyo Young Lee, Jin-Haeng Chung, Yoo Duk Choi, Chang Hun Lee, Lucia Kim, Myoung Ja Chung, Soon Hee Jung, Gou Young Kim, Wan-Seop Kim; Received April 4, 2018 Accepted July 9, 2018 Published online July 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.10 [Accepted]

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