EBV-Positive Gastric Adenocarcinomas: A Distinct Clinicopathologic Entity With a Low Frequency of Lymph Node Involvement

Abstract

Purpose Epstein-Barr virus (EBV) is detected in a substantial subgroup of gastric adenocarcinomas worldwide. We have previously reported that these EBV-positive gastric carcinomas carry distinct genomic aberrations. In the present study, we analyzed a large cohort of EBV-positive and EBV-negative gastric adenocarcinomas for their clinicopathologic features to determine whether they constitute a different clinical entity. Patients and Methods Using a validated polymerase chain reaction/enzyme immunoassay–based prescreening method in combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N = 566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic features collected for the Dutch D1D2 trial. Results EBV-positive gastric carcinomas occurred significantly more frequently in males (P < .0001) and in younger patients (P = .012). Most were of the intestinal type according to the Laurén classification (P = .047) or tubular according to the WHO classification (P = .006) and located in the proximal part of the stomach (P < .0001). A significantly lower tumor-node-metastasis system-stage (P = .026) was observed in the patients with EBV-carrying carcinomas, which was solely explained by less lymph node (LN) involvement (P = .034) in these cases. In addition, a better prognosis, as reflected by a longer disease-free period (P = .04) and a significant better cancer-related survival (P = .02), was observed for these patients, which could be explained by less LN involvement, less residual disease, and younger patient age. Conclusion EBV-carrying gastric adenocarcinomas are a distinct entity of carcinomas, characterized not only by unique genomic aberrations, but also by distinct clinicopathologic features associated with significantly better prognosis.