PROLIFERATIVE COMPARTMENT DEREGULATION IN THE NONNEOPLASTIC COLONIC EPITHELIUM OF FAMILIAL ADENOMATOUS POLYPOSIS

Previous work has shown abnormalities in the proliferative activity of the colorectal mucosa in familial adenomatous polyposis (FAP). Some d oubts remain about the validity of these findings because of difficult ies in excluding adenomatous crypts, particularly in methods using tri tiated 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 con trols using a new monoclonal antibody MIB1 to assay the expression of Ki-67 antigen in routinely processed tissue. The labelling indices wer e 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 ce lls showed a significant shift of the proliferative compartment toward s the luminal surface in the FAP group. Specifically, the labelling in dex was lower in the basal fifth of the polyposis crypts and higher in the two fifths at the luminal surface. These results show that analys is of proliferative activity in FAP is now achievable in routine histo logical material and indicate deregulation of proliferative control in the FAP colonic crypt. This may form a useful diagnostic adjunct to s tandard clinical and molecular genetic techniques, particularly in vie w of the current interest in dietary and pharmacological intervention in sporadic colorectal carcinoma.