MOLECULAR PATHOGENESIS OF ADENOMA AND DIFFERENTIATED ADENOCARCINOMA OF THE STOMACH

Advances in molecular biology have revealed a consistent set of geneti c alterations that may correspond to multistep tumor development. The pathogenesis of adenoma and differentiated adenocarcinoma of the stoma ch are reviewed from a genetic perspective with reference to the color ectal adenoma-carcinoma sequence. The sequential accumulation of genet ic alterations characteristic of the colorectal adenoma-carcinoma sequ ence does not occur between adenoma and differentiated adenocarcinoma of the stomach, although adenomatous polyposis coli (APC) mutation in adenoma, and p53 mutation and loss of heterozygosity (LOH) of DCC (del eted in colorectal cancer) gene in carcinoma are prevalent genetic alt erations. Allelotype, LOH and microsatellite analyses have revealed se veral chromosomal regions of deletion, as well as genetic instability, that accumulate during the development and progression of differentia ted adenocarcinomas. However, these alterations are rarely found in ad enomas of the stomach. These findings suggest that the adenoma-carcino ma sequence is relatively rare in gastric carcinogenesis, and that mos t differentiated adenocarcinomas of the stomach develop through a de n ovo pathway.