Down regulation of gastric and intestinal phenotypic expression in Epstein-Barr virus-associated stomach cancers

Aims: We have previously demonstrated the importance of gastric and intestinal phenotypic expression for stomach carcinogenesis. In this study, we focused on Epstein-Barr virus (EBV)-associated stomach cancers, with special attention to Cdx2. Methods and Results: We evaluated the expression of gastric and intestinal phenotypic markers by immunohistochemistry in 35 EBV-positive [EBV (+)] and 75 EBV-negative [EBV (-)] stomach cancers in Colombia. The lesions were divided phenotypically into gastric (G), gastric-and-intestinal mixed (GI), intestinal (I), and null (N) phenotypes. In the EBV (+) cases, the lesions were divided phenotypically into 9 G (25.7%), 1 GI (2.9%), 3 I (8.6%), and 22 N (62.9%) types. Similarly, the EBV (-) lesions were also classified phenotypically as 15 G (20.0%), 19 GI (25.3%), 24 I (32.0%), and 17 N (22.7%) types. The proportion of N type EBV (+) lesions was higher than for their EBV (-) counterparts (P<0.0001). The expression of Cdx2 and MUC2 was also found to be significantly lower in EBV (+) than in EBV (-) stomach cancers (P=0.0001; P<0.0001). Cdx2 expression in the intestinal metaplastic glands present in non-neoplastic mucosa surrounding EBV (+) lesions was also significantly lower than in EBV (-) tumors (P=0.016) despite no evidence of EBV infection. Conclusions. EBV (+) stomach cancers are characterized by low expression of intestinal phenotype markers, including Cdx2, and only occasional gastric phenotypic expression.