HIGH-FREQUENCY OF KI-RAS AMPLIFICATION AND P53 GENE-MUTATIONS IN ADENOCARCINOMAS OF THE HUMAN ESOPHAGUS

Mutated ras genes have been found to be conspicuously absent from prim ary tumors of the esophagus, although high expression of ras p21 oncop rotein in some esophageal squamous cell carcinomas and mutations of th e Ki- and Ha-ras genes in esophageal carcinoma cell lines have been re ported. In this study, we found amplification of the Ki-ras gene in fo ur of 10 esophageal adenocarcinomas (40%). No such amplification was o bserved among 61 squamous cell carcinomas, one pseudosarcomatous carci noma, and eight esophageal cell lines, nor in six adenocarcinomas of t he stomach. in two samples on which immunohistochemical analysis could be performed, we found overexpression of Ki-ras proteins when compare d with normal samples. This Ki-ras amplification in esophageal tumors did not correlate with any pathological feature of the tumors, with th e survival of the patients, or with the presence of other genetic alte rations. These findings provide the first evidence for amplification o f the Ki-ras gene in human esophageal cancer, which is restricted to a denocarcinomas. We also found that six of eight adenocarcinomas had po int mutations in the p53 gene; this is a considerably higher prevalenc e than that reported for esophageal squamous cell carcinomas. These re sults strongly suggest that esophageal adenocarcinomas differ from squ amous cell carcinomas in their molecular genetic characteristics. (C) 1995 Wiley-Liss, Inc.