Universität zu Köln

Hewitt, L. C., Inam, I. Z., Saito, Y., Yoshikawa, T., Quaas, A., Hoelscher, A., Bollschweiler, E., Fazzi, G. E., Melotte, V., Langley, R. E., Nankivell, M., Cunningham, D., Allum, W., Hutchins, G. G. and Grabsch, H. I. (2018). Epstein-Barr virus and mismatch repair deficiency status differ between oesophageal and gastric cancer: A large multi-centre study. Eur. J. Cancer, 94. S. 104 - 115. OXFORD: ELSEVIER SCI LTD. ISSN 1879-0852

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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 EpsteineBarr 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. (C) 2018 The Authors. Published by Elsevier Ltd.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hewitt, L. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Inam, I. Z. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saito, Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yoshikawa, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoelscher, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bollschweiler, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fazzi, G. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Melotte, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langley, R. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nankivell, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cunningham, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Allum, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hutchins, G. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grabsch, H. I. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-186887
DOI:	10.1016/j.ejca.2018.02.014
Journal or Publication Title:	Eur. J. Cancer
Volume:	94
Page Range:	S. 104 - 115
Date:	2018
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	1879-0852
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SQUAMOUS-CELL CARCINOMA; CLINICAL-PRACTICE GUIDELINES; HIGH-INCIDENCE AREA; MICROSATELLITE-INSTABILITY; DOUBLE-BLIND; OPEN-LABEL; IMMUNOHISTOCHEMISTRY; FLUOROURACIL; CHEMOTHERAPY; EXPRESSION Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18688