Multiple APC mutations in sporadic flat colorectal adenomas

Adenomas are established pre-malignant lesions in colorectal carcinogenesis . To date the adenoma-carcinoma sequence for the development of colorectal carcinoma (CRC) has been based largely on molecular data of exophytic, poly poid-type adenomas, Subsequently, a different type of adenoma has been iden tified: the Bat adenoma, so called for its flat, non-esophytic appearance, making it less likely to be detected during conventional endoscopy, However , due to technological advances in endoscopic methods, flat-type adenomas c an now frequently be detected and are no longer considered rare colorectal lesions. The phenotype of flat colorectal adenomas differs macroscopically and histologically from exophytic adenomas, Flat colorectal adenomas, as a rule, are tubular structures often revealing high-grade dysplasia, irrespec tive of the size or villous component. Flat adenomas have also been recogni sed as precancerous lesions in gastric cancer. Unlike the wealth of clinica l and molecular information available for polypoid (exophytic) adenomas, mo lecular profiles of flat-type lesions have not yet been characterised syste matically and the full clinical significance hereof realised, Previous mole cular investigation of the K-ras gene in Bat colorectal adenomas suggests a distinct pathway in their development. In this study, mutation analysis of the adenomatous polyposis coli (APC) gene using the protein truncation tes t (PIT) in 20 flat colorectal adenomas in a selected group of 16 patients w ithout hereditary predisposition to colorectal cancer, revealed double trun cations of the APC gene in four adenomas. In one of these adenomas a third mutation was detected by DNA sequence analysis.