Journal of Pathology and Translational Medicine

Review

Interpretation of PD-L1 expression in gastric cancer: summary of a consensus meeting of Korean gastrointestinal pathologists: 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; Received February 22, 2024 Accepted March 14, 2024 Published online April 25, 2024; DOI: https://doi.org/10.4132/jptm.2024.03.15 [Epub ahead of print]

57 View
9 Download

Abstract PDF: 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.

Original Article

BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy: Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim; J Pathol Transl Med. 2023;57(6):323-331. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.22

981 View
180 Download

Abstract PDF Supplementary Material: Background
Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations.
Methods
To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype.
Results
Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype.
Conclusions
In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

Review

Molecular Testing for Gastrointestinal Cancer: 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; J Pathol Transl Med. 2017;51(2):103-121. Published online February 19, 2017; DOI: https://doi.org/10.4132/jptm.2017.01.24

17,881 View
893 Download
55 Web of Science
49 Crossref

Abstract PDF

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.

Citations

Citations to this article as recorded by

Chitosan and Its Derivative-Based Nanoparticles in Gastrointestinal Cancers: Molecular Mechanisms of Action and Promising Anticancer Strategies
Zahra Shokati Eshkiki, Fatemeh Mansouri, Amir Reza Karamzadeh, Abolfazl Namazi, Hafez Heydari, Javad Akhtari, Seidamir Pasha Tabaeian, Abolfazl Akbari, Hongda Liu
Journal of Clinical Pharmacy and Therapeutics.2024; 2024: 1. CrossRef
A Standardized Pathology Report for Gastric Cancer: 2nd Edition
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,
Journal of Gastric Cancer.2023; 23(1): 107. CrossRef
A standardized pathology report for gastric cancer: 2nd edition
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,
Journal of Pathology and Translational Medicine.2023; 57(1): 1. CrossRef
Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han Kim, In-Ho Kim, Seung Joo Kang, Miyoung Choi, Baek-Hui Kim, Bang Wool Eom, Bum Jun Kim, Byung-Hoon Min, Chang In Choi, Cheol Min Shin, Chung Hyun Tae, Chung sik Gong, Dong Jin Kim, Arthur Eung-Hyuck Cho, Eun Jeong Gong, Geum Jong Song, Hyeon-Su Im
Journal of Gastric Cancer.2023; 23(1): 3. CrossRef
Influence of location-dependent sex difference on PD-L1, MMR/MSI, and EGFR in colorectal carcinogenesis
Jina Choi, Nayoung Kim, Ryoung Hee Nam, Jin Won Kim, Chin-Hee Song, Hee Young Na, Gyeong Hoon Kang, Alvaro Galli
PLOS ONE.2023; 18(2): e0282017. CrossRef
Comprehensive Analysis of Epigenetic Associated Genes with Differential Gene Expression and Prognosis in Gastric Cancer
Songlin An, Xinbao Li, Bing Li, Yan Li
Combinatorial Chemistry & High Throughput Screening.2023; 26(3): 527. CrossRef
Liquid Biopsy in Advanced Colorectal Cancer: Clinical Applications of Different Analytes
Marco Donatello Delcuratolo, Andrea Modrego-Sánchez, Maristella Bungaro, Beatriz Antón-Pascual, Santiago Teran, Valentina Dipace, Silvia Novello, Rocio Garcia-Carbonero, Francesco Passiglia, Cristina Graválos-Castro
Journal of Molecular Pathology.2023; 4(3): 128. CrossRef
Exosomal circ_0001190 Regulates the Progression of Gastric Cancer via miR-586/SOSTDC1 Axis
Chao Liu, Jing Yang, Fengchi Zhu, Zhiying Zhao, Lixue Gao
Biochemical Genetics.2022; 60(6): 1895. CrossRef
Optimization of pre‐analytical and analytical steps for DNA and RNA analysis of fresh cytology samples
Ana Dolinar, Gašper Grubelnik, Irena Srebotnik‐Kirbiš, Margareta Strojan Fležar, Margareta Žlajpah
Cancer Medicine.2022; 11(21): 4021. CrossRef
Retracted: Connexin 43 upregulation by dioscin‐inhibited gastric cancer metastasis by suppressing PI3K/Akt pathway

Food Science & Nutrition.2022;[Epub] CrossRef
Molecular Pathology of Gastric Cancer
Moonsik Kim, An Na Seo
Journal of Gastric Cancer.2022; 22(4): 264. CrossRef
Case report: Undifferentiated sarcoma with multiple tumors involved in Lynch syndrome: Unexpected favorable outcome to sintilimab combined with chemotherapy
Jiaying Liu, Xiaona Chang, Guixiang Xiao, Jingmin Zhong, Bo Huang, Jiwei Zhang, Beibei Gao, Gang Peng, Xiu Nie
Frontiers in Oncology.2022;[Epub] CrossRef
The SUMO E3 ligase CBX4 is identified as a poor prognostic marker of gastric cancer through multipronged OMIC analyses
Yi Pan, Qingshang Li, Zhijun Cao, Shuliang Zhao
Genes & Diseases.2021; 8(6): 827. CrossRef
Worldwide variation in lynch syndrome screening: case for universal screening in low colorectal cancer prevalence areas
George Kunnackal John, Vipin Das Villgran, Christine Caufield-Noll, Francis Giardiello
Familial Cancer.2021; 20(2): 145. CrossRef
Tamoxifen Downregulates the Expression of Notch1 and DLL1 Genes in MKN-45 Gastric Cancer Cells
Faranak Khanipouyani, Hassan Akrami
Journal of Gastrointestinal Cancer.2021; 52(3): 922. CrossRef
Kallikrein-11, in Association with Coiled-Coil Domain Containing 25, as a Potential Prognostic Marker for Cholangiocarcinoma with Lymph Node Metastasis
Saeranee Siriphak, Ravinnipa Chanakankun, Tanakorn Proungvitaya, Sittiruk Roytrakul, Doungdean Tummanatsakun, Wunchana Seubwai, Molin Wongwattanakul, Siriporn Proungvitaya
Molecules.2021; 26(11): 3105. CrossRef
ISH-based HER2 diagnostics
Josef Rüschoff, Iris Nagelmeier, Bharat Jasani, Oliver Stoss
Der Pathologe.2021; 42(S1): 62. CrossRef
Identification and Analysis of Key Genes Driving Gastric Cancer Through Bioinformatics
Zhao Liu, Shihai Liu, Jing Guo, Libin Sun, Shasha Wang, Yixuan Wang, Wensheng Qiu, Jing Lv
Genetic Testing and Molecular Biomarkers.2021; 25(1): 1. CrossRef
Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker
Francis Yew Fu Tieng, Nadiah Abu, Learn-Han Lee, Nurul-Syakima Ab Mutalib
Diagnostics.2021; 11(3): 544. CrossRef
Metformin attenuates synergic effect of diabetes mellitus and Helicobacter pylori infection on gastric cancer cells proliferation by suppressing PTEN expression
Huibin Lu, Xinwei Han, Jianzhuang Ren, Kewei Ren, Zongming Li, Quanhui Zhang
Journal of Cellular and Molecular Medicine.2021; 25(10): 4534. CrossRef
Recent Advances in the Diagnosis, Staging, Treatment, and Prognosis of Advanced Gastric Cancer: A Literature Review
Zhi-da Chen, Peng-fei Zhang, Hong-qing Xi, Bo Wei, Lin Chen, Yun Tang
Frontiers in Medicine.2021;[Epub] CrossRef
Tumor immune response and immunotherapy in gastric cancer
Yoonjin Kwak, An Na Seo, Hee Eun Lee, Hye Seung Lee
Journal of Pathology and Translational Medicine.2020; 54(1): 20. CrossRef
Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR
Boram Kim, Soo Kyung Nam, Soo Hyun Seo, Kyoung Un Park, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee
Scientific Reports.2020;[Epub] CrossRef
Differential prognostic impact of CD8+ T cells based on human leucocyte antigen I and PD-L1 expression in microsatellite-unstable gastric cancer
Yoonjin Kwak, Jiwon Koh, Yujun Park, Yun Ji Hong, Kyoung Un Park, Hyung-Ho Kim, Do Joong Park, Sang-Hoon Ahn, Woo Ho Kim, Hye Seung Lee
British Journal of Cancer.2020; 122(9): 1399. CrossRef
High-Accuracy Determination of Microsatellite Instability Compatible with Liquid Biopsies
Amanda Bortolini Silveira, François-Clément Bidard, Amélie Kasperek, Samia Melaabi, Marie-Laure Tanguy, Manuel Rodrigues, Guillaume Bataillon, Luc Cabel, Bruno Buecher, Jean-Yves Pierga, Charlotte Proudhon, Marc-Henri Stern
Clinical Chemistry.2020; 66(4): 606. CrossRef
Chitosan: A compound for drug delivery system in gastric cancer-a review
Rana Shafabakhsh, Bahman Yousefi, Zatollah Asemi, Banafsheh Nikfar, Mohammad Ali Mansournia, Jamal Hallajzadeh
Carbohydrate Polymers.2020; 242: 116403. CrossRef
MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link with Novel Immunotherapy
Maria Grazia Rodriquenz, Giandomenico Roviello, Alberto D’Angelo, Daniele Lavacchi, Franco Roviello, Karol Polom
Journal of Clinical Medicine.2020; 9(5): 1427. CrossRef
Theoretical calculations of molecular descriptors for anticancer activities of 1, 2, 3-triazole-pyrimidine derivatives against gastric cancer cell line (MGC-803): DFT, QSAR and docking approaches
Rhoda Oyeladun Oyewole, Abel Kolawole Oyebamiji, Banjo Semire
Heliyon.2020; 6(5): e03926. CrossRef
Identification of a Clinical Cutoff Value for Multiplex KRASG12/G13 Mutation Detection in Colorectal Adenocarcinoma Patients Using Digital Droplet PCR, and Comparison with Sanger Sequencing and PNA Clamping Assay
Kyung Ha Lee, Tae Hee Lee, Min Kyung Choi, In Sun Kwon, Go Eun Bae, Min-Kyung Yeo
Journal of Clinical Medicine.2020; 9(7): 2283. CrossRef
PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs
Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Keun-Wook Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee
Cancer Research and Treatment.2020; 52(3): 661. CrossRef
Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants
Nathália de Angelis de Carvalho, Bianca Naomi Niitsuma, Vanessa Nascimento Kozak, Felipe D’almeida Costa, Mariana Petaccia de Macedo, Bruna Elisa Catin Kupper, Maria Letícia Gobo Silva, Maria Nirvana Formiga, Sahlua Miguel Volc, Samuel Aguiar Junior, Eden
Cancers.2020; 12(7): 1848. CrossRef
Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis
Junhui Yu, Shan Li, Jing Guo, Zhengshui Xu, Jianbao Zheng, Xuejun Sun
Cell Death & Disease.2020;[Epub] CrossRef
YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2
Qingli Bie, Xiaozhe Li, Shiqi Liu, Xiao Yang, Zhenwen Qian, Rou Zhao, Xiaobei Zhang, Bin Zhang
International Journal of Clinical Oncology.2020; 25(12): 2055. CrossRef
ISH-basierte HER2-Diagnostik
Josef Rüschoff, Iris Nagelmeier, Bharat Jasani, Oliver Stoss
Der Pathologe.2020; 41(6): 606. CrossRef
Histone Deacetylase Inhibitor Trichostatin A Suppresses Cell Proliferation and Induces Apoptosis by Regulating the PI3K/AKT Signalling Pathway in Gastric Cancer Cells
Xinli An, Zekun Wei, Botian Ran, Hao Tian, Hongyu Gu, Yan Liu, Hongjuan Cui, Shunqin Zhu
Anti-Cancer Agents in Medicinal Chemistry.2020; 20(17): 2114. CrossRef
Role of Her-2 in Gastrointestinal Tumours beyond Gastric Cancer: A Tool for Precision Medicine
Csongor G. Lengyel, Baker Habeeb, Shah Z. Khan, Khalid El Bairi, Sara C. Altuna, Sadaqat Hussain, Syed Ayub Mazher, Dario Trapani, Angelica Petrillo
Gastrointestinal Disorders.2020; 3(1): 1. CrossRef
Next-generation Sequencing in the Management of Gastric and Esophageal Cancers
Jill C. Rubinstein, Norman G. Nicolson, Nita Ahuja
Surgical Clinics of North America.2019; 99(3): 511. CrossRef
Molecular profile in Paraguayan colorectal cancer patients, towards to a precision medicine strategy
Tania Fleitas-Kanonnikoff, Carolina Martinez‐Ciarpaglini, Josefina Ayala, Cinthia Gauna, Rita Denis, Ita Yoffe, Silvia Sforza, María Teresa Martínez, Alicia Pomata, Maider Ibarrola‐Villava, Sipan Arevshatyan, Verónica Burriel, Diego Boscá, Oscar Pastor, A
Cancer Medicine.2019; 8(6): 3120. CrossRef
Human epidermal growth factor receptor 2-positive digestive tumors
Anna D. Wagner, Berna C. Özdemir, Josef Rüschoff
Current Opinion in Oncology.2019; 31(4): 354. CrossRef
Assessing molecular subtypes of gastric cancer: microsatellite unstable and Epstein-Barr virus subtypes. Methods for detection and clinical and pathological implications
Carolina Martinez-Ciarpaglini, Tania Fleitas-Kanonnikoff, Valentina Gambardella, Marta Llorca, Cristina Mongort, Regina Mengual, Gema Nieto, Lara Navarro, Marisol Huerta, Susana Rosello, Desamparados Roda, Noelia Tarazona, Samuel Navarro, Gloria Ribas, An
ESMO Open.2019; 4(3): e000470. CrossRef
Current and future molecular diagnostics of gastric cancer
Rachel Sin-Yu Choi, Wing Yin Xenia Lai, Lok Ting Claire Lee, Wing Lam Christa Wong, Xiao Meng Pei, Hin Fung Tsang, Joel Johnson Leung, William Chi Shing Cho, Man Kee Maggie Chu, Elaine Yue Ling Wong, Sze Chuen Cesar Wong
Expert Review of Molecular Diagnostics.2019; 19(10): 863. CrossRef
Clinicopathologic significance of human leukocyte antigen class I expression in patients with stage II and III gastric cancer
Yujun Park, Jiwon Koh, Yoonjin Kwak, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee
Cancer Immunology, Immunotherapy.2019; 68(11): 1779. CrossRef
Development and Validation of an Easy-to-Implement, Practical Algorithm for the Identification of Molecular Subtypes of Gastric Cancer: Prognostic and Therapeutic Implications
Jiwon Koh, Keun-Wook Lee, Soo Kyung Nam, An Na Seo, Ji-Won Kim, Jin Won Kim, Do Joong Park, Hyung-Ho Kim, Woo Ho Kim, Hye Seung Lee
The Oncologist.2019; 24(12): e1321. CrossRef
Mechanisms and Therapy for Cancer Metastasis to the Brain
Federica Franchino, Roberta Rudà, Riccardo Soffietti
Frontiers in Oncology.2018;[Epub] CrossRef
Status of programmed death-ligand 1 expression in sarcomas
Hyung Kyu Park, Mingi Kim, Minjung Sung, Seung Eun Lee, Yu Jin Kim, Yoon-La Choi
Journal of Translational Medicine.2018;[Epub] CrossRef
Design and synthesis of near-infrared fluorescence-enhancement probes for the cancer-specific enzyme hNQO1
Changyu Zhang, Bei-Bei Zhai, Tao Peng, Zelin Zhong, Lianbin Xu, Qiang-Zhe Zhang, Lu-Yuan Li, Long Yi, Zhen Xi
Dyes and Pigments.2017; 143: 245. CrossRef
Progress in the treatment of advanced gastric cancer
Zheyu Song, Yuanyu Wu, Jiebing Yang, Dingquan Yang, Xuedong Fang
Tumor Biology.2017; 39(7): 101042831771462. CrossRef
Pathologische Einteilung und Diagnostik des Ösophagus- und Magenkarzinoms
S. Förster, A. Tannapfel
Der Gastroenterologe.2017; 12(5): 394. CrossRef
NR4A1-induced increase in the sensitivity of a human gastric cancer line to TNFα-mediated apoptosis is associated with the inhibition of JNK/Parkin-dependent mitophagy
Hongzhu Yan, Feng Xiao, Jue Zou, Chengmin Qiu, Weiwei Sun, Minmin Gu, Li Zhang
International Journal of Oncology.2017;[Epub] CrossRef

First
Prev
Page of 1
Next
Last

Search