Cell cycle regulators, APC/beta-catenin, NF-kappa B and Epstein-Barr virus in gastric carcinomas

Aims: To evaluate the clinicopathological value of cell cycle regulators, the Writ pathway, the NF-beta B pathway and Epstein-Barr virus (EBV) and to assess their relationships in gastric carcinoma. Methods: We investigated cell cycle regulators (p53, p21, Rb), APC, beta-catenin and NF-kappa B using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma. Results: p53 overexpression was more frequently observed in advanced gastric carcinoma and lymph node metastasis than in early carcinoma or in the absence of metastasis (p < 0.05). p21 loss was positively correlated with APC loss, but inversely correlated with beta-catenin nuclear accumulation and NF-kappa B positivity (p < 0.05). EBV positive gastric carcinomas were located in the upper third of the stomach, and more were of the diffuse or mixed types than the EBV negative group (p < 0.05). EBV infection was positively correlated with p21 loss and APC loss and inversely correlated with beta-catenin alteration (p < 0.05). In multivariate analysis, patient age, TNM stage and p53 were independent prognostic factors for gastric carcinoma. Conclusions: p53 status is a prognostic marker for gastric carcinoma. p21, APC, beta-catenin and NF-kappa B may be functionally interrelated in gastric carcinogenesis. Loss of p21 and APC may be involved in the carcinogenesis of EBV positive gastric carcinomas.