Over expression of the p53 tumor suppressor gene product in esophageal and gastric carcinomas

Abstract

p53 protein has been reported as frequently overexpressed in esophageal and gastric carcinomas. However, the correlation between p53 protein expression and clinico-pathological features of the tumors is debated in this heterogeneous group of cancers. The aim of this study was to establish the prevalence of p53 protein overexpression in a series of resected esophageal squamous carcinomas (n = 78), adenocarcinomas developed on Barrett's esophagus (n = 20), adenocarcinomas of the cardia (n = 36), and adenocarcinomas of the antrum (n = 30), and to correlate this expression with the clinico-pathological and flow-cytometric characteristics of the tumors. Immunohistochemical staining was performed on frozen sections with a monoclonal antibody directed against wild type and mutated p53 protein (Pab 1801). An adjacent frozen specimen was used for flow cytometric determination of the DNA-ploidy and S phase fraction. p53 protein nuclear expression was detected in 76% of esophageal squamous carcinomas, in 75% of adenocarcinomas developed in Barretts esophagus, in 56% of adenocarcinomas of the cardia, and in 27% of adenocarcinomas of the antrum. Only the number of positive adenocarcinomas of the antrum was significantly lower when compared to the other three types of tumors (p = 0.001). No significant correlation was observed between p53 protein expression and most of the clinico-pathological and flow-cytometric parameters (sex, age, tobacco smoking, chronic alcohol consumption, size of the tumor, grade of differentiation, depth of infiltration, presence of lymph node metastases, UICC stage, DNA-ploidy, S phase fraction). p53 protein expression was more frequent in Lauren's intestinal adenocarcinomas (67%) when compared to the diffuse type tumors (24%) (p = 0.002). Our results confirm that overexpression of p53 protein is a common feature of esophageal and gastric carcinomas. The high prevalence of p53 protein overexpression found in cardiac adenocarcinoma when compared to antral adenocarcinoma reinforces the hypothesis of distinct carcinogenetic mechanisms in these two cancers. In particular the lack of correlation between p53 expression and tumor stage suggests that p53 protein overexpression is an early event in these tumors.