{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:07:39Z","timestamp":1782922059229,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21cm0106502h0006"],"award-info":[{"award-number":["JP21cm0106502h0006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epstein\u2010Barr virus (EBV) is one of the major drivers of gastric carcinogenesis. EBV infection is established before tumour initiation and is generally maintained throughout tumour development; however, the significance of EBV in tumour maintenance and progression remains to be elucidated. Here, we report eight cases of EBV\u2010associated gastric carcinoma (EBVaGC) with intratumoural heterogenous expression of EBV\u2010encoded small RNA (<jats:italic>EBER<\/jats:italic>), a highly expressed latent gene of EBV, and demonstrate clinicopathological characteristics of these rare cases. By performing detailed histological assessment of <jats:italic>EBER<\/jats:italic>\u2010positive and \u2010negative components of each case, detection of EBV genome in tumour cells by fluorescence <jats:italic>in situ<\/jats:italic> hybridisation, <jats:italic>TP73<\/jats:italic> methylation analysis, whole exome sequencing, and targeted gene panel sequencing, we identified tumours in two patients to be collision tumours of different origins. In the other six patients, some genetic\/epigenetic alterations were shared between <jats:italic>EBER<\/jats:italic>\u2010positive and \u2010negative components, suggesting that EBV was eliminated from tumour cells during progression. Interestingly, in both tumour types, programmed death ligand 1 and intratumoural infiltration of CD8+ T lymphocytes were lower in <jats:italic>EBER<\/jats:italic>\u2010negative than in <jats:italic>EBER<\/jats:italic>\u2010positive components, suggesting an immunogenic role of EBV. To the best of our knowledge, this study is the first to demonstrate the detailed histological features and genetic\/epigenetic alterations in EBVaGC with heterogenous <jats:italic>EBER<\/jats:italic> expression; the loss of EBV may benefit tumour progression and immune evasion and might be clinically important for selecting treatment strategies for such cancers. \u00a9 2023 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6067","type":"journal-article","created":{"date-parts":[[2023,2,18]],"date-time":"2023-02-18T13:33:29Z","timestamp":1676727209000},"page":"124-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Loss of viral genome with altered immune microenvironment during tumour progression of <scp>Epstein\u2010Barr virus<\/scp>\u2010associated gastric carcinoma"],"prefix":"10.1002","volume":"260","author":[{"given":"Atsushi","family":"Kondo","sequence":"first","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0196-5643","authenticated-orcid":false,"given":"Aya","family":"Shinozaki\u2010Ushiku","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine The University of Tokyo  Tokyo Japan"},{"name":"Division of Integrative Genomics, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4172-4892","authenticated-orcid":false,"given":"Hirofumi","family":"Rokutan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate School of Medicine The University of Tokyo  Tokyo 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