Phenotypic and genotypic characteristics of aberrant crypt foci in human colorectal mucosa.

ABSTRACT

Aberrant crypt foci (ACF) in colorectal mucosa are proposed to be the earliest morphological lesion in the development of neoplasia, but their characteristics remain controversial. We therefore studied the epithelial phenotype and genotype of ACF from patients with familial adenomatous polyposis (FAP) and of sporadic ACF by evaluating glycoprotein markers associated with neoplasia (lectins Dolichus biflorus agglutinin and peanut agglutinin; monoclonal antibody CA 19-9 against sialyl Lewis-a blood group substance), expression of proliferating cell nuclear antigen, and ras proto-oncogene mutations. The utility of the markers was established by comparing adenomas and hyperplastic polyps. Most FAP ACF resembled adenomas and were found to differ from sporadic ACF in their high frequency of dysplasia, staining with Dolichus biflorus agglutinin, expression of sialyl Lewis-a, proliferation in the epithelium of upper crypts, and low frequency of ras gene mutations (P = .04 to < .0000001). By contrast, sporadic ACF and a subset of FAP ACF had phenotypic characteristics resembling hyperplastic polyps but usually had ras mutations, which were inversely related to dysplasia (P = .00009). Our findings suggest that "aberrant crypt focus" is a generic term analogous to "polyp" and requires further histopathologic, phenotypic, or genotypic classification into dysplastic and heteroplastic (hetero = other, plasia = form) types. Dysplastic ACF represent potential precursors to colorectal adenomas and adenocarcinomas, but heteroplastic ACF appear to be associated, rather than precursor, lesions.