Epstein-Barr virus involvement in gastric cancer: biomarker for lymph node metastasis.

EBV involvement in gastric cancer is characterized by episomal monoclonality, high antibody titers, EBV encoded small RNA and EBV nuclear antigen 1 expression in all tumor cells, and in the intramucosal stage, by a unique morphology. EBV involvement varies by population (approximately 7% of gastric cancers in Japan and >15% in Western countries), sex, histological type, and tumor location. The present study compares frequency of lymph node metastasis (LNM) between 170 EBV-positive and 1590 EBV-negative gastric cancer cases in Japan by level of invasiveness. Frequency of LNM increased with increasing depth of invasiveness but was consistently and significantly greater for EBV-negative cases (P = 0.0018). In particular, there were no instances of LNM among 75 EBV-positive cases as compared with 53 among 562 EBV-negative cases restricted to the mucosa and submucosa (odds ratio, 0; 95% confidence limits, 0-0.20). The finding suggests that genetic control of metastasis may differ between EBV-related and other gastric cancers. Also, the possibility that EBV-positive, noninvasive gastric cancers may not require lymph node dissection suggests that routine assay of biopsy specimens for EBV involvement could be important in populations, like that of Japan, where early gastric cancers are seen frequently.