Host inflammatory response predicts survival of patients with Epstein-Barr virus-associated gastric carcinoma.

Abstract

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. 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. 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). 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.