{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:14:19Z","timestamp":1779297259532,"version":"3.51.4"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background and Objectives: Gastric cancer (GC) is one of the most commonly diagnosed cancers and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy. A classification that uses on-slide biomarkers and formalin-fixed and paraffin-embedded (FFPE) tissue is preferable to comprehensive genomic analysis. In 2016, Setia and colleagues proposed an on-slide classification; however, this is not in widespread use. We propose a modification of this classification that has six subgroups: GC associated with Epstein\u2013Barr virus (GC EBV+), GC with mismatch-repair deficiency (GC dMMR), GC with epithelial\u2013mesenchymal transformation (GC EMT), GC with chromosomal instability (GC CIN), CG that is genomically stable (GC GS) and GC not otherwise specified (GC NOS). This classification also has a provision for biomarkers for current or emerging targeted therapies (Her2, PD-L1 and Claudin18.2). Here, we assess the implementation and feasibility of this inclusive working classification. Materials and Methods: We constructed a tissue microarray library from a cohort of 79 resection cases from FFPE tissue archives. We used a restricted panel of on-slide markers (EBER, MMR, E-cadherin, beta-catenin and p53), defined their interpretation algorithms and assigned each case to a specific molecular subtype. Results: GC EBV(+) cases were 6%, GC dMMR cases were 20%, GC EMT cases were 14%, GC CIN cases were 23%, GC GS cases were 29%, and GC NOS cases were 8%. Conclusions: This working classification uses markers that are widely available in histopathology and are easy to interpret. A diagnostic subgroup is obtained for 92% of the cases. The proportion of cases in each subgroup is in keeping with other published series. Widescale implementation appears feasible. A study using endoscopic biopsies is warranted.<\/jats:p>","DOI":"10.3390\/cancers16010055","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T08:16:02Z","timestamp":1703146562000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Implementing an On-Slide Molecular Classification of Gastric Cancer: A Tissue Microarray Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Simona","family":"Costache","sequence":"first","affiliation":[{"name":"Pathology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020021 Bucharest, Romania"},{"name":"Poundbury Cancer Institute, Dorchester DT1 3BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"de Havilland","sequence":"additional","affiliation":[{"name":"Poundbury Cancer Institute, Dorchester DT1 3BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Diaz McLynn","sequence":"additional","affiliation":[{"name":"Poundbury Cancer Institute, Dorchester DT1 3BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Sajin","sequence":"additional","affiliation":[{"name":"Pathology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020021 Bucharest, Romania"},{"name":"Pathology Department, University Emergency Hospital, 050098 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelina","family":"Baltan","sequence":"additional","affiliation":[{"name":"Pathology Department, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020021 Bucharest, Romania"},{"name":"Poundbury Cancer Institute, Dorchester DT1 3BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Wedden","sequence":"additional","affiliation":[{"name":"Cancer Diagnostic Quality Assurance Services (CADQAS), Dorchester DT1 3BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"D\u2019Arrigo","sequence":"additional","affiliation":[{"name":"Poundbury Cancer Institute, Dorchester DT1 3BJ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13073-017-0484-3","article-title":"Actionable Gene-Based Classification toward Precision Medicine in Gastric Cancer","volume":"9","author":"Ichikawa","year":"2017","journal-title":"Genome Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2014). Comprehensive Molecular Characterization of Gastric Adenocarcinoma. Nature, 513, 202\u2013209.","DOI":"10.1038\/nature13480"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nm.3850","article-title":"Molecular Analysis of Gastric Cancer Identifies Subtypes Associated with Distinct Clinical Outcomes","volume":"21","author":"Cristescu","year":"2015","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1038\/ncomms6477","article-title":"Genomic Landscape and Genetic Heterogeneity in Gastric Adenocarcinoma Revealed by Whole-Genome Sequencing","volume":"5","author":"Wong","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/modpathol.2016.55","article-title":"A Protein and MRNA Expression-Based Classification of Gastric Cancer","volume":"29","author":"Setia","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/PAS.0000000000000756","article-title":"High-Throughput Protein and MRNA Expression\u2013Based Classification of Gastric Cancers Can Identify Clinically Distinct Subtypes, Concordant with Recent Molecular Classifications","volume":"41","author":"Ahn","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhao, C., Feng, Z., He, H., Zang, D., Du, H., Huang, H., Du, Y., He, J., Zhou, Y., and Nie, Y. (2020). Protein Expression-Based Classification of Gastric Cancer by Immunohistochemistry of Tissue Microarray. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238836"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/jso.25792","article-title":"Gastric Cancer Molecular Classification and Adjuvant Therapy: Is There a Different Benefit According to the Subtype?","volume":"121","author":"Ramos","year":"2020","journal-title":"J. Surg. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The Two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma: An Attempt at a Histo-Clinical Classification","volume":"64","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Costache, S., Sajin, M., Wedden, S., and D\u2019arrigo, C. (2023). A Consolidated Working Classification of Gastric Cancer for Histopathologists (Review). Biomed. Rep., 19.","DOI":"10.3892\/br.2023.1640"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41571-021-00492-2","article-title":"Biomarker-Targeted Therapies for Advanced-Stage Gastric and Gastro-Oesophageal Junction Cancers: An Emerging Paradigm","volume":"18","author":"Nakamura","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Alexa, M., Hasenburg, A., and Battista, M.J. (2021). The TCGA Molecular Classification of Endometrial Cancer and Its Possible Impact on Adjuvant Treatment Decisions. Cancers, 13.","DOI":"10.3390\/cancers13061478"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40661-016-0035-4","article-title":"New Classification of Endometrial Cancers: The Development and Potential Applications of Genomic-Based Classification in Research and Clinical Care","volume":"3","author":"Talhouk","year":"2016","journal-title":"Gynaecol. Oncol. Res. Pract."},{"key":"ref_14","unstructured":"Organisation Mondiale de la Sant\u00e9, and Centre International de Recherche sur le Cancer (2020). World Health Organization Classification of Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_15","unstructured":"Organisation Mondiale de la Sant\u00e9, and Centre International de Recherche sur le Cancer (2019). World Health Organization Classification of Tumours, International Agency for Research on Cancer. [5th ed.]."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3322\/caac.21388","article-title":"The Eighth Edition AJCC Cancer Staging Manual: Continuing to Build a Bridge from a Population-Based to a More \u201cPersonalized\u201d Approach to Cancer Staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1309\/MMAU-0QYH-7BHA-W8C2","article-title":"Guidelines for Interpreting EBER In Situ Hybridization and LMP1 Immunohistochemical Tests for Detecting Epstein-Barr Virus in Hodgkin Lymphoma","volume":"117","author":"Gulley","year":"2002","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/cjp2.120","article-title":"Heterogenous Loss of Mismatch Repair (MMR) Protein Expression: A Challenge for Immunohistochemical Interpretation and Microsatellite Instability (MSI) Evaluation","volume":"5","author":"McCarthy","year":"2019","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Burandt, E., L\u00fcbbersmeyer, F., Gorbokon, N., B\u00fcscheck, F., Luebke, A.M., Menz, A., Kluth, M., Hube-Magg, C., Hinsch, A., and H\u00f6flmayer, D. (2021). E-Cadherin Expression in Human Tumors: A Tissue Microarray Study on 10,851 Tumors. Biomark. Res., 9.","DOI":"10.1186\/s40364-021-00299-4"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1097\/01.pap.0000194628.58501.71","article-title":"The Diagnostic Value of \u03b2-Catenin Immunohistochemistry","volume":"12","author":"Montgomery","year":"2005","journal-title":"Adv. Anat. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S123","DOI":"10.1097\/PGP.0000000000000488","article-title":"Interpretation of P53 Immunohistochemistry in Endometrial Carcinomas: Toward Increased Reproducibility","volume":"38","author":"Ronnett","year":"2019","journal-title":"Int. J. Gynecol. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/j.1365-2559.2008.03028.x","article-title":"Assessment of a HER2 Scoring System for Gastric Cancer: Results from a Validation Study","volume":"52","author":"Hofmann","year":"2008","journal-title":"Histopathology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.3748\/wjg.v22.i19.4619","article-title":"HER2 Testing in Gastric Cancer: An Update","volume":"22","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13000-018-0696-x","article-title":"Physical Basis of the \u2018Magnification Rule\u2019 for Standardized Immunohistochemical Scoring of HER2 in Breast and Gastric Cancer","volume":"13","author":"Scheel","year":"2018","journal-title":"Diagn. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e14589","DOI":"10.1200\/JCO.2017.35.15_suppl.e14589","article-title":"Development of the Combined Positive Score (CPS) for the Evaluation of PD-L1 in Solid Tumors with the Immunohistochemistry Assay PD-L1 IHC 22C3 PharmDx","volume":"35","author":"Kulangara","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0344-0338(11)80878-2","article-title":"New Elements for an Updated Classification of the Carcinomas of the Stomach","volume":"191","author":"Carneiro","year":"1995","journal-title":"Pathol.-Res. Pract."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1097\/01.MP.0000076980.73826.C0","article-title":"Lymphocyte-Rich Gastric Cancer: Associations with Epstein-Barr Virus, Microsatellite Instability, Histology, and Survival","volume":"16","author":"Grogg","year":"2003","journal-title":"Mod. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Shi, J., Yang, X., Wang, X., Luo, Y., Zhou, W., Luo, H., Bianba, Z., Nima, Z., Wang, Q., and Wang, H. (2022). Prevalence of Epstein\u2013Barr Virus Infection and Mismatch Repair Protein Deficiency and the Correlation of Immune Markers in Tibetan Patients with Gastric Cancer. BioMed Res. Int., 2022.","DOI":"10.1155\/2022\/2684065"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"195","DOI":"10.2350\/07-07-0316.1","article-title":"Epstein-Barr Virus (EBV)-Encoded RNA: Automated In-Situ Hybridization (ISH) Compared with Manual ISH and Immunohistochemistry for Detection of EBV in Pediatric Lymphoproliferative Disorders","volume":"12","author":"Fanaian","year":"2009","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13027-022-00469-5","article-title":"EBV Persistence in Gastric Cancer Cases Conventionally Classified as EBER-ISH Negative","volume":"17","author":"Siciliano","year":"2022","journal-title":"Infect. Agents Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1385\/1-59259-081-0:301","article-title":"Molecular Methods for Detecting Epstein-Barr Virus (Part I): In Situ Hybridization to Epstein-Barr Virus-Encoded RNA (EBER) Transcripts","volume":"Volume 49","author":"Fan","year":"2000","journal-title":"Molecular Pathology Protocols"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Tavakoli, A., Monavari, S.H., Solaymani Mohammadi, F., Kiani, S.J., Armat, S., and Farahmand, M. (2020). Association between Epstein-Barr Virus Infection and Gastric Cancer: A Systematic Review and Meta-Analysis. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07013-x"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mundo, L., Ambrosio, M.R., Picciolini, M., Lo Bello, G., Gazaneo, S., Del Porro, L., Lazzi, S., Navari, M., Onyango, N., and Granai, M. (2017). Unveiling Another Missing Piece in EBV-Driven Lymphomagenesis: EBV-Encoded MicroRNAs Expression in EBER-Negative Burkitt Lymphoma Cases. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00229"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"583463","DOI":"10.3389\/fonc.2020.583463","article-title":"EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives","volume":"10","author":"Sun","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13027-023-00489-9","article-title":"Assessing Epstein\u2013Barr Virus in Gastric Cancer: Clinicopathological Features and Prognostic Implications","volume":"18","author":"Li","year":"2023","journal-title":"Infect. Agents Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.canlet.2008.03.022","article-title":"CpG Island Methylator Phenotype (CIMP) in Cancer: Causes and Implications","volume":"268","author":"Teodoridis","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/PAP.0000000000000015","article-title":"HER2 in Breast Cancer: A Review and Update","volume":"21","author":"Krishnamurti","year":"2014","journal-title":"Adv. Anat. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/cncr.29046","article-title":"Polymerase \u03b5 (POLE) Mutations in Endometrial Cancer: Clinical Outcomes and Implications for Lynch Syndrome Testing: POLE Mutations and Endometrial Cancer","volume":"121","author":"Billingsley","year":"2015","journal-title":"Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Stanland, L.J., and Luftig, M.A. (2020). The Role of EBV-Induced Hypermethylation in Gastric Cancer Tumorigenesis. Viruses, 12.","DOI":"10.3390\/v12111222"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/j.molonc.2016.09.004","article-title":"Concordance of Immune Checkpoints within Tumor Immune Contexture and Their Prognostic Significance in Gastric Cancer","volume":"10","author":"Dai","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1093\/jnci\/djx213","article-title":"Immune Activation and Benefit from Avelumab in EBV-Positive Gastric Cancer","volume":"110","author":"Panda","year":"2018","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"761909","DOI":"10.1100\/2012\/761909","article-title":"Genetic Aspects of Gastric Cancer Instability","volume":"2012","author":"Hudler","year":"2012","journal-title":"Sci. World J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.3390\/encyclopedia2030106","article-title":"Mismatch Repair Deficiency and Microsatellite Instability","volume":"2","year":"2022","journal-title":"Encyclopedia"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/1746-1596-8-114","article-title":"Usefulness and Limitations of E-Cadherin and \u03b2-Catenin in the Classification of Breast Carcinomas in Situ with Mixed Pattern","volume":"8","author":"Gomes","year":"2013","journal-title":"Diagn. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2020227118","DOI":"10.1073\/pnas.2020227118","article-title":"Parsing \u03b2-Catenin\u2019s Cell Adhesion and Wnt Signaling Functions in Malignant Mammary Tumor Progression","volume":"118","author":"Buechel","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"R792","DOI":"10.1016\/S0960-9822(01)00473-0","article-title":"Adhesion Signaling: How \u03b2-Catenin Interacts with Its Partners","volume":"11","author":"Gottardi","year":"2001","journal-title":"Curr. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/his.12869","article-title":"E-Cadherin Immunohistochemistry in Breast Pathology: Uses and Pitfalls","volume":"68","author":"Schnitt","year":"2016","journal-title":"Histopathology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/modpathol.3800362","article-title":"E-Cadherin Alterations in Atypical Lobular Hyperplasia and Lobular Carcinoma in Situ of the Breast","volume":"18","author":"Mastracci","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/32918","article-title":"E-Cadherin Germline Mutations in Familial Gastric Cancer","volume":"392","author":"Guilford","year":"1998","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e386","DOI":"10.1016\/S1470-2045(20)30219-9","article-title":"Hereditary Diffuse Gastric Cancer: Updated Clinical Practice Guidelines","volume":"21","author":"Blair","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_51","first-page":"27","article-title":"E-cadherin associated protein expression and its significance in invasive lobular carcinoma and invasive ductal carcinoma of breast","volume":"30","author":"Han","year":"2001","journal-title":"Zhonghua Bing Li Xue Za Zhi"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10549-011-1860-0","article-title":"Cadherin\u2013Catenin Complex Dissociation in Lobular Neoplasia of the Breast","volume":"132","author":"Morrogh","year":"2012","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s10585-005-4578-8","article-title":"Frequent Loss of Membranous E-Cadherin in Gastric Cancers: A Cross-Talk with Wnt in Determining the Fate of \u03b2-Catenin","volume":"22","author":"Cheng","year":"2005","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Huiping, C., Kristjansdottir, S., Jonasson, J.G., Magnusson, J., Egilsson, V., and Ingvarsson, S. (2001). Alterations of E-Cadherin and \u03b2-Catenin in Gastric Cancer. BMC Cancer, 1.","DOI":"10.1186\/1471-2407-1-16"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/S0140-6736(23)00732-8","article-title":"Claudin-18.2 Targeting by Zolbetuximab: Results of SPOTLIGHT in Perspective","volume":"401","author":"Derks","year":"2023","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"TPS365","DOI":"10.1200\/JCO.2022.40.4_suppl.TPS365","article-title":"Zolbetuximab + CAPOX versus CAPOX in First-Line Treatment of Claudin18.2+\/HER2\u2212 Advanced\/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: GLOW Phase 3 Study","volume":"40","author":"Shah","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.annonc.2021.02.005","article-title":"FAST: A Randomised Phase II Study of Zolbetuximab (IMAB362) plus EOX versus EOX Alone for First-Line Treatment of Advanced CLDN18.2-Positive Gastric and Gastro-Oesophageal Adenocarcinoma","volume":"32","author":"Sahin","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Choi, S., Park, S., Kim, H., Kang, S.Y., Ahn, S., and Kim, K.-M. (2022). Gastric Cancer: Mechanisms, Biomarkers, and Therapeutic Approaches. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030543"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s12672-022-00479-0","article-title":"PD-L1 Expression in EBV Associated Gastric Cancer: A Systematic Review and Meta-Analysis","volume":"13","author":"Lima","year":"2022","journal-title":"Discov. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"17588359221083048","DOI":"10.1177\/17588359221083049","article-title":"The Dawn of Precision Medicine in Diffuse-Type Gastric Cancer","volume":"14","author":"Ooki","year":"2022","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s13046-019-1121-3","article-title":"A Subset of Diffuse-Type Gastric Cancer Is Susceptible to MTOR Inhibitors and Checkpoint Inhibitors","volume":"38","author":"Fukamachi","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"152881","DOI":"10.1016\/j.prp.2020.152881","article-title":"High PD-L1 Expression in Gastric Cancer (GC) Patients and Correlation with Molecular Features","volume":"216","author":"Liu","year":"2020","journal-title":"Pathol.-Res. Pract."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Gu, L., Chen, M., Guo, D., Zhu, H., Zhang, W., Pan, J., Zhong, X., Li, X., Qian, H., and Wang, X. (2017). PD-L1 and Gastric Cancer Prognosis: A Systematic Review and Meta-Analysis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182692"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S1470-2045(16)00175-3","article-title":"Pembrolizumab for Patients with PD-L1-Positive Advanced Gastric Cancer (KEYNOTE-012): A Multicentre, Open-Label, Phase 1b Trial","volume":"17","author":"Muro","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-Line Nivolumab plus Chemotherapy versus Chemotherapy Alone for Advanced Gastric, Gastro-Oesophageal Junction, and Oesophageal Adenocarcinoma (CheckMate 649): A Randomised, Open-Label, Phase 3 Trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/1\/55\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:39:42Z","timestamp":1760132382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/1\/55"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["cancers16010055"],"URL":"https:\/\/doi.org\/10.3390\/cancers16010055","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]}}}