Intramucosal carcinomas of the stomach: phenotypic expression and loss of heterozygosity at microsatellites linked to the APC gene.

Evaluation of the role of somatic genetic alterations in cancer development is best performed by examining small tumors in the earlier stages of carcinogenesis. We examined the relationship between allelic deletions of 4 microsatellites linked to the adenomatous polyposis coli (APC) gene and differential histogenetical phenotypes in 34 intramucosal carcinomas of the stomach, of which, structurally, 24 cases were the gland-forming type (so-called "intestinal type") and 10 were the diffuse type. Using mucin and immunohistochemical staining techniques specific for gastric- and intestinal-type mucins, the phenotype of each tumor was histogenetically classified as exclusively gastric, predominantly gastric, predominantly intestinal or exclusively intestinal. There was generally a free combination between structural types and phenotypic mucin expression. Allelic deletions were detected in 6 carcinomas of the exclusively intestinal phenotype. The incidence of allelic deletions was significantly higher in the predominantly and exclusively intestinal phenotypes (6/16, 37.5%) than in the predominantly and exclusively gastric phenotypes (0/18) (p = 0.0060, Fisher's test). Taking the high frequency of allelic deletions in 5q in invasive stomach carcinomas, the present study suggests that genetic alteration in this region is a very early event in stomach carcinomas with intestinal differentiation but a relatively late event in those with gastric differentiation.