Epstein-Barr virus and microsatellite instability in gastric carcinogenesis.

Little information is available concerning the relationship between transforming viruses and microsatellite instability (MSI). We evaluated Epstein-Barr virus (EBV) using in situ hybridization for EBV-encoded small RNAs and MSI using the polymerase chain reaction in surgically resected gastric cancer. The study subjects included 298 consecutive cases of solitary gastric carcinoma, 63 gastric carcinomas in young patients (</=30 years old), 64 cases of gastric cancer coexisting with gastric adenoma in a single lesion, 26 cases of gastric remnant cancer, and 98 carcinomas from 47 patients with synchronous multiple gastric carcinomas. There was no overlapping case among these subsets of gastric cancer. None of these 549 gastric carcinomas demonstrated both EBV positivity and MSI positivity. Furthermore, the EBV-positive and the MSI-positive cases showed a mutually negative association in all subsets of gastric cancer. 5.7% of consecutive solitary gastric carcinomas were EBV positive, and 9.7% were MSI positive. EBV was positive in 1.6% of gastric cancers coexisting with gastric adenoma, 12.7% of younger patients, 28.6% of gastric remnant cancer with previous gastrectomy for benign disease, and 14.5% of synchronous cancers without adenoma. MSI was found in 1.6% of younger patients, 18.8% of gastric cancers coexisting with gastric adenoma, 25% of gastric remnant cancer with previous gastrectomy for gastric cancer, and in 53.3% of synchronous gastric carcinomas having gastric adenoma remote from the cancer. In conclusion, the carcinogenic roles of EBV and MSI may be different in terms of each subset of gastric cancer. EBV and MSI may contribute to functionally equivalent pathways in gastric carcinogenesis.