Background & aims: Lymphoepithelioma-like carcinoma (LELC) is a rare subtype of gastric carcinoma (GC) with a better survival rate than other GCs; most cases of LELC are associated with Epstein-Barr virus (EBV) infection. We investigated whether the survival advantage of LELC is related to the EBV infection itself or to associated inflammatory immune responses.
Methods: From 1994 to 2008, 123 EBV-associated GCs were identified and compared with 405 EBV-negative GCs. EBV-associated GCs were subclassified, based on the pattern of host inflammatory immune responses, into 3 histologic subtypes: typical LELC (n = 53, 43.1%), Crohn's disease-like lymphocytic reaction (CLR) (n = 52, 42.3%), and conventional adenocarcinoma (n = 18, 14.6%). Patients with curatively resected EBV-negative GC were controls. Univariate and multivariate analyses were used, with Bonferroni correction.
Results: Patients with EBV-associated GC had tumors of proximal location, lower N stage (P < .0001), and lower T stage (P = .02) and were older than controls (P = .0003). Upon univariate analysis, patients with EBV-associated GC had longer survival times than controls (P < .004); this difference was not significant in a multivariate analysis with Cox proportional hazards. Stratification of EBV-associated GCs by host cellular immune responses showed that patients with LELC and LELC+CLR have significantly longer overall survival time (hazard ratio, 0.09 and 0.42, respectively) and disease-free survival (hazard ratio, 0.05 and 0.46, respectively; P < .02).
Conclusions: Prognosis of EBV-associated GCs depends on the patient's inflammatory response. The definition of LELC should be expanded to include EBV-associated GCs with CLR because these have a prognosis similar to LELC.
Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.