p53 overexpression is different in Epstein-Barr virus-associated and Epstein-Barr virus-negative carcinoma

Aims: Epstein-Barr virus (EBV) is associated with a subset of gastric and head and neck carcinomas. While p53 mutation and overexpression is common in gastric cancer, in nasopharyngeal carcinoma p53 is overexpressed yet mutation is uncommon, leading to a proposed viral mechanism of p53 upregulation. We examined the expression of p53 protein in 18 EBV-associated gastric carcinomas (EBV-GA) and compared it with 29 age and sex matched EBV- negative gastric carcinomas (EBV₀-GA) and 23 non-nasopharyngeal EBV- associated carcinomas (EBV-CAs) arising from various head and neck regions. Methods and results: Using two monoclonal antibodies (DO7 and PAb1801) with microwave pre-treatment, the p53 protein was scored according to the intensity and percentage of positive cells. The EBV₀-GA showed a clear cut bimodal distribution of p53 levels, with either homogeneous intense staining of most tumour nuclei, or only very weak expression in a few cells. Nearly all the EBV-GA and EBV-CAs showed a weak to moderate p53 expression, characterized by heterogeneous intensity of staining in a variable proportion of tumour cells. Conclusions: The difference in p53 levels in the EBV₀-GA and EBV-GA is statistically significant. The heterogeneous level of p53 in the EBV-GA and EBV-CAs and its difference from the EBV₀-GA is suggestive of a nonmutational mechanism of p53 upregulation and underscores the role of the virus in the oncogenic pathway.