Cell cycle regulators, APC/β-catenin, NF-κB and Epstein-Barr virus in gastric carcinomas

SummaryAimsTo evaluate the clinicopathological value of cell cycle regulators, the Wnt pathway, the NF-βB pathway and Epstein-Barr virus (EBV) and to assess their relationships in gastric carcinoma.MethodsWe investigated cell cycle regulators (p53, p21, Rb), APC, β-catenin and NF-κB using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma.Resultsp53 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 β-catenin nuclear accumulation and NF-KB 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 β-catenin alteration (p < 0.05). In multivariate analysis, patient age, TNM stage and p53 were independent prognostic factors for gastric carcinoma.Conclusionsp53 status is a prognostic marker for gastric carcinoma. p21, APC, β-catenin and NF-κB may be functionally interrelated in gastric carcinogenesis. Loss of p21 and APC may be involved in the carcinogenesis of EBV positive gastric carcinomas.