Background & aims: Small intestinal carcinomas are rare but occur with increased incidence in Crohn's disease. The aim of this study was to elucidate the genetic alterations.
Methods: Mutations and deletions involved in colorectal carcinoma were studied in sporadic and Crohn's-associated intestinal carcinomas and precursors.
Results: c-K-ras mutations were present in all four sporadic carcinomas with contiguous adenomas, in only 18% without adenomas (P = 0.01), in 43% of Crohn's-associated carcinomas, and in 14% of dysplasias. Overexpression of p53 gene product and/or 17p allelic loss were present in 47% of sporadic carcinomas and 33% of contiguous adenomas and in 71% of Crohn's-associated carcinomas and 43% of dysplasias. In contrast, allelic losses of 5q (adenomatous polyposis coli [APC] gene region) and 18q (deleted in colorectal cancer [DCC] gene region) were rare. DNA replication errors (RERs) were present in 13% of sporadic carcinomas and in the carcinoma and dysplasias of 1 patient with Crohn's disease (14%), but mutations in the transforming growth factor beta type II receptor (TGFbeta RII) gene were absent.
Conclusions: Accumulation of ras and p53 alterations occurs during the adenoma/dysplasia-carcinoma sequence in small intestinal carcinogenesis, but a ras-independent pathway may also exist. The infrequent loss of the APC and DCC regions and the absence of TGFbeta RII gene mutation in RER-positive neoplasms contrast with colorectal carcinogenesis.