Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress through the chromosomal instability pathway

The hyperplastic polyposis syndrome is characterized by the presence within the colon of multiple large hyperplastic polyps. We describe a case of hyp erplastic polyposis syndrome associated with two synchronous carcinomas, on e of which arises within a pre-existing hyperplastic lesion. Comparative ge nomic hybridization was used to determine genetic changes in both carcinoma s and several associated hyperplastic lesions. Microsatellite analysis at f ive loci was performed on carcinomas and representative hyperplastic polyps , and p53 status was analyzed by immunohistochemistry. Both carcinomas show ed multiple genetic aberrations, including high level gains of 8q and 13q, and loss of 5q. These changes were not seen in the hyperplastic polyps. Mic rosatellite instability was not seen in the carcinomas, four separate hyper plastic polyps, the hyperplastic polyp with mild adenomatous change associa ted with the carcinoma, or a separate serrated adenoma, Allelic imbalance i n the cancers at D5S346 and D17S938 suggested allelic loss of both p53 and APC, as well as at the loci D13S263, D13S174, D13S159, and D18S49, An early invasive carcinoma in one hyperplastic polyp stained for p53 protein, but the associated hyperplastic polyp was negative. In this case, neoplastic pr ogression followed the typical genetic pathway of common colorectal carcino ma and occurred synchronously with mutation of p53.