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

From the Department of Pathology, VU University Medical Center, Amsterdam; and the Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands

Address reprint requests to Elisabeth Bloemena, MD, PhD, Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands; e-mail: e.bloemena{at}vumc.nl

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.

Supported by Dutch Cancer Society grant VU99-1990.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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