Proliferative compartment deregulation in the non-neoplastic colonic epithelium of familial adenomatous polyposis

Abstract

Previous work has shown abnormalities in the proliferative activity of the colorectal mucosa in familial adenomatous polyposis (FAP). Some doubts remain about the validity of these findings because of difficulties in excluding adenomatous crypts, particularly in methods using tritiated thymidine, bromodeoxyuridine, and ornithine decarboxylase. The proliferative activity of the epithelium in colonic resections from 20 FAP patients was compared with that of age, sex, and site matched controls using a new monoclonal antibody MIB1 to assay the expression of Ki-67 antigen in routinely processed tissue. The labelling indices were very similar in the polyposis and control cases (25.5 (1.4)% and 26.7 (1.7)% respectively) but analysis of the distribution of labelled cells showed a significant shift of the proliferative compartment towards the luminal surface in the FAP group. Specifically, the labelling index was lower in the basal fifth of the polyposis crypts and higher in the two fifths at the luminal surface. These results show that analysis of proliferative activity in FAP is now achievable in routine histological material and indicate deregulation of proliferative control in the FAP colonic crypt. This may form a useful diagnostic adjunct to standard clinical and molecular genetic techniques, particularly in view of the current interest in dietary and pharmacological intervention in sporadic colorectal carcinoma.