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

• DOI: 10.1016/j.ejca.2018.02.014
• Publication Date: 2018-03-20T11:32:58Z
• Authors: L.C. Hewitt; I.Z. Inam; Y. Saito; T. Yoshikawa; A. Quaas; A. Hoelscher; E. Bollschweiler; G.E. Fazzi; V. Melotte; R.E. Langley; M. Nankivell; D. Cunningham; W. Allum; G.G. Hutchins; H.I. Grabsch
• Keywords: Adult; Male; 0301 basic medicine; HIGH-INCIDENCE AREA; Epstein-Barr Virus Infections; Epsteine-Barr virus; Esophageal Neoplasms; DNA mismatch repair; EMC OR-01; 610; RANDOMIZED PHASE-3 TRIAL; DNA Mismatch Repair; Article; Epstein–Barr virus; DOUBLE-BLIND; 03 medical and health sciences; MICROSATELLITE-INSTABILITY; SDG 3 - Good Health and Well-being; Stomach Neoplasms; Biomarkers, Tumor; Humans; ddc:610; Aged; ddc:610; Tumor; Oesophageal cancer; COLON-CANCER; NONPOLYPOSIS COLORECTAL-CANCER; Middle Aged; OPEN-LABEL; PD-1 BLOCKADE; 3. Good health; Microsatellite instability; Female; Microsatellite Instability; SQUAMOUS-CELL CARCINOMA; CLINICAL-PRACTICE GUIDELINES; Gastric cancer; Biomarkers

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.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.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).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.