- A standardized pathology report for gastric cancer: 2nd edition
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Young Soo Park, Myeong-Cherl Kook, Baek-hui Kim, Hye Seung Lee, Dong-Wook Kang, Mi-Jin Gu, Ok Ran Shin, Younghee Choi, Wonae Lee, Hyunki Kim, In Hye Song, Kyoung-Mee Kim, Hee Sung Kim, Guhyun Kang, Do Youn Park, So-Young Jin, Joon Mee Kim, Yoon Jung Choi, Hee Kyung Chang, Soomin Ahn, Mee Soo Chang, Song-Hee Han, Yoonjin Kwak, An Na Seo, Sung Hak Lee, Mee-Yon Cho
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J Pathol Transl Med. 2023;57(1):1-27. Published online January 15, 2023
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DOI: https://doi.org/10.4132/jptm.2022.12.23
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- The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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- Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis
Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim Cancer Research and Treatment.2024; 56(1): 219. CrossRef - Microscopic tumor mapping of post-neoadjuvant therapy pancreatic cancer specimens to predict post-surgical recurrence: A prospective cohort study
Yeshong Park, Yeon Bi Han, Jinju Kim, MeeYoung Kang, Boram Lee, Eun Sung Ahn, Saemi Han, Haeryoung Kim, Hee-Young Na, Ho-Seong Han, Yoo-Seok Yoon Pancreatology.2024;[Epub] CrossRef - Effect of Neoadjuvant Chemotherapy on Tumor-Infiltrating Lymphocytes in Resectable Gastric Cancer: Analysis from a Western Academic Center
Elliott J. Yee, Danielle Gilbert, Jeffrey Kaplan, Sachin Wani, Sunnie S. Kim, Martin D. McCarter, Camille L. Stewart Cancers.2024; 16(7): 1428. CrossRef - Pathological Interpretation of Gastric Tumors in Endoscopic Submucosal Dissection
Jung Yeon Kim Journal of Digestive Cancer Research.2023; 11(1): 15. CrossRef - Histopathology of Gastric Cancer
Baek-hui Kim, Sung Hak Lee The Korean Journal of Helicobacter and Upper Gastrointestinal Research.2023; 23(2): 143. CrossRef - Endoscopic submucosal dissection hands-on training with artificial mucosal layer EndoGEL
Tae-Se Kim, Jun Haeng Lee Journal of Innovative Medical Technology.2023; 1(1): 5. CrossRef
- Prediction of TP53 mutations by p53 immunohistochemistry and their prognostic significance in gastric cancer
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Hye Jung Hwang, Soo Kyung Nam, Hyunjin Park, Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Woo Ho Kim, Hye Seung Lee
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J Pathol Transl Med. 2020;54(5):378-386. Published online July 1, 2020
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DOI: https://doi.org/10.4132/jptm.2020.06.01
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- Background
Recently, molecular classifications of gastric cancer (GC) have been proposed that include TP53 mutations and their functional activity. We aimed to demonstrate the correlation between p53 immunohistochemistry (IHC) and TP53 mutations as well as their clinicopathological significance in GC.
Methods Deep targeted sequencing was performed using surgical or biopsy specimens from 120 patients with GC. IHC for p53 was performed and interpreted as strong, weak, or negative expression. In 18 cases (15.0%) with discrepant TP53 mutation and p53 IHC results, p53 IHC was repeated.
Results Strong expression of p53 was associated with TP53 missense mutations, negative expression with other types of mutations, and weak expression with wild-type TP53 (p<.001). The sensitivity for each category was 90.9%, 79.0%, and 80.9%, and the specificity was 95.4%, 88.1%, and 92.3%, respectively. The TNM stage at initial diagnosis exhibited a significant correlation with both TP53 mutation type (p=.004) and p53 expression status (p=.029). The Kaplan-Meier survival analysis for 109 stage II and III GC cases showed that patients with TP53 missense mutations had worse overall survival than those in the wild-type and other mutation groups (p=.028). Strong expression of p53 was also associated with worse overall survival in comparison to negative and weak expression (p=.035).
Conclusions Results of IHC of the p53 protein may be used as a simple surrogate marker of TP53 mutations. However, negative expression of p53 and other types of mutations of TP53 should be carefully interpreted because of its lower sensitivity and different prognostic implications.
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- Tumor immune response and immunotherapy in gastric cancer
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Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee
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J Pathol Transl Med. 2020;54(1):20-33. Published online November 1, 2019
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DOI: https://doi.org/10.4132/jptm.2019.10.08
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- Remarkable developments in immuno-oncology have changed the landscape of gastric cancer (GC) treatment. Because immunotherapy intervenes with tumor immune response rather than directly targeting tumor cells, it is important to develop a greater understanding of tumor immunity. This review paper summarizes the tumor immune reaction and immune escape mechanisms while focusing on the role of T cells and their co-inhibitory signals, such as the immune checkpoint molecules programmed death-1 and programmed deathligand 1 (PD-L1). This paper also describes past clinical trials of immunotherapy for patients with GC and details their clinical implications. Strong predictive markers are essential to improve response to immunotherapy. Microsatellite instability, Epstein-Barr virus, PD-L1 expression, and tumor mutational burden are now regarded as potent predictive markers for immunotherapy in patients with GC. Novel immunotherapy and combination therapy targeting new immune checkpoint molecules such as lymphocyte-activation gene 3, T cell immunoglobulin, and mucin domain containing-3, and indoleamine 2,3-dioxygenase have been suggested, and trials are ongoing to evaluate their safety and efficacy. Immunotherapy is an important treatment option for patients with GC and has great potential for improving patient outcome, and further research in immuno-oncology should be carried out.
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Zai-Sheng Ye, Miao Zheng, Qin-Ying Liu, Yi Zeng, Sheng-Hong Wei, Yi Wang, Zhi-Tao Lin, Chen Shu, Qiu-Hong Zheng, Lu-Chuan Chen World Journal of Gastroenterology.2021; 27(21): 2871. CrossRef - Immunotherapy of gastric cancer: Past, future perspective and challenges
Jun Xie, Liping Fu, Li Jin Pathology - Research and Practice.2021; 218: 153322. CrossRef - Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases
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Wen-jun Zhang, Ce-gui Hu, Zheng-ming Zhu, Hong-liang Luo Biomedicine & Pharmacotherapy.2020; 125: 109844. CrossRef - Current status and future potential of predictive biomarkers for immune checkpoint inhibitors in gastric cancer
Byung Woog Kang, Ian Chau ESMO Open.2020; 5(4): e000791. CrossRef - Is ramucirumab still the only second-line treatment in metastatic gastric cancer?
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- Cytologic Diagnosis of Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features and Its Impact on the Risk of Malignancy in the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience
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Milim Kim, Joung Eun Kim, Hyun Jeong Kim, Yul Ri Chung, Yoonjin Kwak, So Yeon Park
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J Pathol Transl Med. 2018;52(3):171-178. Published online April 3, 2018
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DOI: https://doi.org/10.4132/jptm.2018.04.03
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Abstract
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- Background
This study was performed to analyze cytologic diagnosis of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and its impact on the risk of malignancy (ROM) in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).
Methods Five thousand five hundred and forty-nine cases of thyroid fine-needle aspiration cytology (FNAC) diagnosed between 2012 and 2014 were included in this study. Diagnostic categories based on TBSRTC were compared with final surgical diagnoses, and the ROM in each category was calculated both when NIFTP was included in malignant lesions and when excluded from malignant lesions.
Results Of the 5,549 thyroid FNAC cases, 1,891 cases underwent surgical resection. In final diagnosis, 1,700 cases were revealed as papillary thyroid carcinoma (PTC), and 25 cases were reclassified as NIFTP. The cytologic diagnoses of NIFTP were non-diagnostic in one, benign in five, atypia of undetermined significance (AUS) in 14, follicular neoplasm in two, and suspicious for malignancy in three cases. Collectively, NIFTP/encapsulated follicular variant of PTC (EFVPTC) were more frequently classified as benign, AUS, or follicular neoplasm and less frequently categorized as malignant compared to conventional PTCs. Exclusion of NIFTP from malignant diagnoses resulted in a slight decrease in malignancy rates in non-diagnostic, benign, AUS, follicular neoplasm, and suspicious for malignancy categories without any statistical significance.
Conclusions The decrease in the ROM was not significant when NIFTP was excluded from malignant lesions. In thyroid FNACs, NIFTP/EFVPTCs were mostly classified into indeterminate categories. Therefore, it might be feasible to separate NIFTP/EFVPTC from conventional PTC on FNAC to guide clinicians to conservative management for patients with NIFTP/EFVPTC.
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- Spatial transcriptomics reveals prognosis‐associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment
Kai Yan, Qing‐Zhi Liu, Rong‐Rong Huang, Yi‐Hua Jiang, Zhen‐Hua Bian, Si‐Jin Li, Liang Li, Fei Shen, Koichi Tsuneyama, Qing‐Ling Zhang, Zhe‐Xiong Lian, Haixia Guan, Bo Xu Clinical and Translational Medicine.2024;[Epub] CrossRef - Cytological features of “Non-invasive follicular tumour with papillary like nuclear features” – A single institutional experience in India
K Amita, HB Rakshitha, M Sanjay, Prashantha Kalappa Journal of Cytology.2023; 40(1): 28. CrossRef - Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary‐like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review
Sevgiye Kaçar Özkara, Gupse Turan Diagnostic Cytopathology.2023; 51(12): 758. CrossRef - Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features Is Not a Cytological Diagnosis, but It Influences Cytological Diagnosis Outcomes: A Systematic Review and Meta-Analysis
Elina Haaga, David Kalfert, Marie Ludvíková, Ivana Kholová Acta Cytologica.2022; 66(2): 85. CrossRef - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
Hee Young Na, So Yeon Park Journal of Pathology and Translational Medicine.2022; 56(6): 319. CrossRef - Usage and Diagnostic Yield of Fine-Needle Aspiration Cytology and Core Needle Biopsy in Thyroid Nodules: A Systematic Review and Meta-Analysis of Literature Published by Korean Authors
Soon-Hyun Ahn Clinical and Experimental Otorhinolaryngology.2021; 14(1): 116. CrossRef - Comprehensive DNA Methylation Profiling Identifies Novel Diagnostic Biomarkers for Thyroid Cancer
Jong-Lyul Park, Sora Jeon, Eun-Hye Seo, Dong Hyuck Bae, Young Mun Jeong, Yourha Kim, Ja Seong Bae, Seon-Kyu Kim, Chan Kwon Jung, Yong Sung Kim Thyroid.2020; 30(2): 192. CrossRef - Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: A systematic review and meta‐analysis
Huy Gia Vuong, Hanh Thi Tuyet Ngo, Andrey Bychkov, Chan Kwon Jung, Trang Huyen Vu, Kim Bach Lu, Kennichi Kakudo, Tetsuo Kondo Cancer Cytopathology.2020; 128(4): 238. CrossRef - Noninvasive follicular neoplasm with papillary like nuclear features: A comprehensive analysis with a diagnostic algorithm
Chanchal Rana, Shreyamsa Manjunath, Pooja Ramakant, Kulranjan Singh, Suresh Babu, Anand Mishra Diagnostic Cytopathology.2020; 48(4): 330. CrossRef - Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features and the risk of malignancy in The Bethesda System for the Reporting of Thyroid Cytopathology
Danielle Elliott Range, Xiaoyin “Sara” Jiang Diagnostic Cytopathology.2020; 48(6): 531. CrossRef - Did Introducing a New Category of Thyroid Tumors (Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features) Decrease the Risk of Malignancy for the Diagnostic Categories in the Bethesda System for Reporting Thyroid Cytopathology?
Janusz Kopczyński, Agnieszka Suligowska, Kornelia Niemyska, Iwona Pałyga, Agnieszka Walczyk, Danuta Gąsior-Perczak, Artur Kowalik, Kinga Hińcza, Ryszard Mężyk, Stanisław Góźdź, Aldona Kowalska Endocrine Pathology.2020; 31(2): 143. CrossRef - High risk of malignancy in cases with atypia of undetermined significance on fine needle aspiration of thyroid nodules even after exclusion of NIFTP
Sevgiye Kaçar Özkara, Büşra Yaprak Bayrak, Gupse Turan Diagnostic Cytopathology.2020; 48(11): 986. CrossRef - The importance of risk of neoplasm as an outcome in cytologic‐histologic correlation studies on thyroid fine needle aspiration
Yu‐Hsin Chen, Kristen L. Partyka, Rae Dougherty, Harvey M. Cramer, Howard H. Wu Diagnostic Cytopathology.2020; 48(12): 1237. CrossRef - Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses
Hee Young Na, Jae Hoon Moon, June Young Choi, Hyeong Won Yu, Woo-Jin Jeong, Yeo Koon Kim, Ji-Young Choe, So Yeon Park, Paula Soares PLOS ONE.2020; 15(11): e0241597. CrossRef - How is noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) shaping the way we interpret thyroid cytology?
Michiya Nishino Journal of the American Society of Cytopathology.2019; 8(1): 1. CrossRef - Cytological Diagnoses Associated with Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features According to the Bethesda System for Reporting Thyroid Cytopathology: A Systematic Review and Meta-Analysis
Massimo Bongiovanni, Luca Giovanella, Francesco Romanelli, Pierpaolo Trimboli Thyroid.2019; 29(2): 222. CrossRef - Preoperative Diagnostic Categories of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features in Thyroid Core Needle Biopsy and Its Impact on Risk of Malignancy
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Khurram Shafique, Virginia A. LiVolsi, Kathleen Montone, Zubair W. Baloch Endocrine Pathology.2018; 29(4): 339. CrossRef
- Molecular Testing for Gastrointestinal Cancer
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Hye Seung Lee, Woo Ho Kim, Yoonjin Kwak, Jiwon Koh, Jeong Mo Bae, Kyoung-Mee Kim, Mee Soo Chang, Hye Seung Han, Joon Mee Kim, Hwal Woong Kim, Hee Kyung Chang, Young Hee Choi, Ji Y. Park, Mi Jin Gu, Min Jin Lhee, Jung Yeon Kim, Hee Sung Kim, Mee-Yon Cho
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J Pathol Transl Med. 2017;51(2):103-121. Published online February 19, 2017
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DOI: https://doi.org/10.4132/jptm.2017.01.24
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- With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.
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- Effects of Fixation and Storage of Human Tissue Samples on Nucleic Acid Preservation
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Soo Kyung Nam, Joon Im, Yoonjin Kwak, Nayoung Han, Kyung Han Nam, An Na Seo, Hye Seung Lee
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Korean J Pathol. 2014;48(1):36-42. Published online February 25, 2014
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DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.36
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- Background
Because of recent advances in the molecular diagnosis of cancer patients, tissue quality has become more important in daily practice. MethodsTo evaluate the effects of fixative, duration of fixation, decalcification, and storage periods on nucleic acid integrity, DNA and RNA were extracted from gastrointestinal cancer tissue. The yield and purity were analyzed, and polymerase chain reaction (PCR) for glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 60 bp), β-actin (148 bp), and human growth hormone (hGH; 434 bp) and real-time reverse transcription-PCR for β-actin (97 bp) were performed. ResultsAll formalin-fixed paraffin-embedded (FFPE) and methacarn-fixed paraffin-embedded (MFPE) samples tested positive for GAPDH and β-actin by PCR. hGH was successfully detected in all MFPE samples, but in only 46.7% of the FFPE samples. Prolonged formalin fixation resulted in fewer GAPDH and β-actin PCR products, and amplification of hGH was not successful. The PCR and reverse transcription-PCR results were significantly affected by the duration of decalcification. The yield, purity, and integrity of mRNA progressively decreased with increased storage periods of paraffin blocks. ConclusionsFixation and storage should therefore be standardized in order to improve the quality of molecular pathologic diagnosis.
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- Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists
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Soomin Ahn, Yoonjin Kwak, Gui Young Kwon, Kyoung-Mee Kim, Moonsik Kim, Hyunki Kim, Young Soo Park, Hyeon Jeong Oh, Kyoungyul Lee, Sung Hak Lee, Hye Seung Lee
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Received February 22, 2024 Accepted March 14, 2024 Published online April 25, 2024
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DOI: https://doi.org/10.4132/jptm.2024.03.15
[Epub ahead of print]
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Abstract
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- Nivolumab plus chemotherapy in the first-line setting has demonstrated clinical efficacy in patients with human epidermal growth factor receptor 2–negative advanced or metastatic gastric cancer, and is currently indicated as a standard treatment. Programmed death-ligand 1 (PD-L1) expression is an important biomarker for predicting response to anti–programmed death 1/PD-L1 agents in several solid tumors, including gastric cancer. In the CheckMate-649 trial, significant clinical improvements were observed in patients with PD-L1 combined positive score (CPS) ≥ 5, determined using the 28-8 pharmDx assay. Accordingly, an accurate interpretation of PD-L1 CPS, especially at a cutoff of 5, is important. The CPS method evaluates both immune and tumor cells and provides a comprehensive assessment of PD-L1 expression in the tumor microenvironment of gastric cancer. However, CPS evaluation has several limitations, one of which is poor interobserver concordance among pathologists. Despite these limitations, clinical indications relying on PD-L1 CPS are increasing. In response, Korean gastrointestinal pathologists held a consensus meeting for the interpretation of PD-L1 CPS in gastric cancer. Eleven pathologists reviewed 20 PD-L1 slides with a CPS cutoff close to 5, stained with the 28-8 pharmDx assay, and determined the consensus scores. The issues observed in discrepant cases were discussed. In this review, we present cases of gastric cancer with consensus PD-L1 CPS. In addition, we briefly touch upon current practices and clinical issues associated with assays used for the assessment of PD-L1 expression in gastric cancer.
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