Aims and methods: p53 tumor suppressor gene is involved in the development of esophageal cancer. However, its role is not precisely defined in the two types of cancer, squamous cell carcinoma and adenocarcinoma developed in Barrett's esophagus. The aim of this work was to compare the frequency and type of mutation of the p53 gene and the expression of the p53 protein in a series of 21 squamous cell carcinomas and 27 adenocarcinomas of the esophagus in a single institution. p53 protein accumulation was assessed by immunohistochemistry with the monoclonal antibody PAb 1801. The mutations of exons 5 to 8 of p53 gene were detected by denaturating gradient gel electrophoresis, and sequenced.
Results: A mutation of the p53 gene and/or an accumulation of the p53 protein were found in 85% of squamous cell carcinomas and 92% of adenocarcinomas, respectively. The profile of mutations differed with the type of tumor; large predominance of transitions on CpG dinucleotides in adenocarcinomas suggesting an endogenous mechanism, high percentage of transversions in squamous cell carcinomas suggesting a direct effect of carcinogens present in tobacco and alcohol.
Conclusion: Mutation of the p53 gene is a very frequent event in the two types of esophageal cancer. The mechanism responsible for these mutations is different in squamous cell carcinomas and adenocarcinomas developed in Barrett's esophagus.