Loss of p16/CDKN2A protein in Epstein-Barr virus-associated gastric carcinoma.

We examined the expression of p16, the CDKN2A gene product, in EBV-associated gastric carcinomas (EBV-GCs). EBV-GCs were identified by detecting EBV-encoded small RNA (EBER) using an in situ hybridization assay of paraffin-embedded tissue. Two non-EBV-GC cases for each EBV-GC case were selected, matched for age, sex, tumor location, and depth of invasion. After excluding cases without sufficient tissue samples for immunohistochemical analysis, 54 EBV-GC and 117 non-EBV-GC cases were available for the present study. The loss of p16 expression was more frequently observed in EBV-GCs (89%) than non-EBV-GC cases (32%; p < 0.001). Among non-EBV-GC cases, the loss of p16 expression was more frequent in female cases (57%) than male cases (29%) (p = 0.042). Expression of p16 was not related to the location of tumor, clinical stage of tumor, age, or prognosis of the patients. In conclusion, the present study suggests that the loss of p16-related cell cycle regulation may be associated with the development of EBV-GC.