TY  - JOUR
A1  - Hewitt, Lindsay C.
A1  - Inam, Imran Z.
A1  - Saito, Yuichi
A1  - Yoshikawa, Takaki
A1  - Quaas, Alexander
A1  - Hölscher, Arnulf H.
A1  - Bollschweiler, Elfriede
A1  - Fazzi, Gregorio E.
A1  - Melotte, Veerle
A1  - Langley, Ruth Elizabeth
A1  - Nankivell, Matthew
A1  - Cunningham, David
A1  - Allum, William
A1  - Hutchins, Gordon G.
A1  - Grabsch, Heike Irmgard
T1  - Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer : a large multi-centre study
T2  - European journal of cancer
N2  - 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.
KW  - Oesophageal cancer
KW  - Gastric cancer
KW  - DNA mismatch repair
KW  - Microsatellite instability
KW  - Epstein–Barr virus
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/48615
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-486156
SN  - 1879-0852
SN  - 1879-2995
SN  - 0959-8049
SN  - 0014-2964
N1  - © 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/).
VL  - 94
SP  - 104
EP  - 114
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -