Recently, alterations of p53 gene in gastric cancer have been reported by several authors, but the role of p53-gene alterations in early step of carcinogenesis of gastric cancer remains unclear. To assess whether p53 expression is an early event in the carcinogenesis of gastric cancer, 402 gastric tumors (14 hyperplastic polyps, 48 gastric adenomas, 340 gastric cancers) were analyzed by immunohistochemistry using the specific antibody, PAb1801, against p53 oncoprotein. Five (15%) of 34 adenomas and 110 (32%) of 340 gastric cancers showed a definite positive nuclear staning for p53 protein. In contrast, the anti-p53 MAb did not show any specific staining in normal gastric epithelial cells, intestinal metaplasia or hyperplastic polyps. Out of nine adenomas showing mild dysplasia, only one tumor (11%) showed p53 expression. In contrast, 4 (16%) of 25 adenomas showing moderate dysplasia revealed positive p53 expression. In addition, positive p53 staining was not found in adenomas less than 1 cm in diameter, but five (25%) of 20 adenomas 1 cm or more in diameter showed definite p53-staining. In this way, the positive-p53 tissue status in adenomas was correlated with the dysplastic grade and size of adenomas. The incidence of positive-p53 immunoreaction in the differentiated type of cancers was 35% and showed no relation to wall invasion. On the contrary, p53 expression in the undifferentiated type of m-cancers, in which tumor invasion was limited to the mucosal layers, was detected in only one (5%) of 21 cases. Among undifferentiated type of gastric cancer, however, deeply invasive cancers showed higher p53-positive rate, as compared with m-cancer. These results may suggest p53 gene activation at a relatively early stage of the adenoma-carcinoma sequence, leading to the development of some differentiated adenocarcinomas in the stomach.

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