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Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study

Hewitt, LC; Inam, IZ; Saito, Y; Yoshikawa, T; Quaas, A; Hoelscher, A; Bollschweiler, E; ... Grabsch, HI; + view all (2018) Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study. European Journal of Cancer , 94 pp. 104-114. 10.1016/j.ejca.2018.02.014. Green open access

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Abstract

BACKGROUND: Oesophageal (OeC) and gastric (GC) cancer patients are treated with similar multimodal therapy and have poor survival. There remains an urgent clinical need to identify biomarkers to individualise patient management and improve outcomes. Therapy with immune checkpoint inhibitors has shown promising results in other cancers. Proposed biomarkers to predict potential response to immune checkpoint inhibitors include DNA mismatch repair (MMR) and/or Epstein-Barr virus (EBV) status. The aim of this study was to establish and compare EBV status and MMR status in large multi-centre series of OeC and GC. METHODS: EBV was assessed by EBV-encoded RNA (EBER) in situ hybridisation and MMR protein expression by immunohistochemistry (IHC) in 988 OeC and 1213 GC from multiple centres. In a subset of OeC, microsatellite instability (MSI) was tested in parallel with MMR IHC. RESULTS: Frequency of MMR deficiency (MMRdef) and MSI was low in OeC (0.8% and 0.6%, respectively) compared with GC (10.3%). None of the OeCs were EBER positive in contrast to 4.8% EBER positive GC. EBV positive GC patients were younger (p = 0.01), more often male (p = 0.001) and had a better overall survival (p = 0.012). MMRdef GC patients were older (p = 0.001) and showed more often intestinal-type histology (p = 0.022). CONCLUSIONS: This is the largest study to date indicating that EBV and MMRdef do not play a role in OeC carcinogenesis in contrast to GC. The potential clinical usefulness of determining MMRdef/EBV status to screen patients for eligibility for immune-targeting therapy differs between OeC and GC patients.

Type: Article
Title: Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ejca.2018.02.014
Publisher version: http://doi.org/10.1016/j.ejca.2018.02.014
Language: English
Additional information: Copyright © 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: DNA mismatch repair, Epstein–Barr virus, Gastric cancer, Microsatellite instability, Oesophageal cancer
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10046994
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