ALTERED MUCIN CORE PEPTIDE IMMUNOREACTIVITY IN THE COLON POLYP-CARCINOMA SEQUENCE

Altered mucin glycosylation occurs in colonic adenomas and can correla te with risk for malignant transformation. The purpose of this study w as to determine if immunoreactivity of core tandem repeat peptides of specific mucin genes correlates with histopathologic criteria of malig nant potential in the colon. Expression of MUC1, MUC2, and MUC3 core t andem repeat proteins was examined in specimens of normal mucosa (n = 20), hyperplastic polyps (n = 10), adenomatous polyps (n = 89), and in vasive cancer (n = 19). An immunohistochemical scoring system that tak es into account specimen heterogeneity and yields an integrated numeri cal score subject to statistical analysis was used. RNA message levels from tubular and tubulovillous adenomas (n = 13), normal colon (n = 1 2), and moderately differentiated adenocarcinomas (n = 8) were determi ned using RNA slot blot analysis with mucin-specific cDNA probes. MUC1 staining was rarely present in normal colon. MUC2 immunoreactivity wa s limited to goblet cells in most normal colonic crypts, and MUC3 stai ning was weakly expressed in the upper crypt regions only. In comparis on with normal and hyperplastic specimens, MUC1 and MUC3 immunoreactiv ity scores were significantly increased in adenomas of increasing vill ous histology, size, and dysplasia. MUC2 scores were significantly inc reased in adenomas of greater villous histology and size. Comparable M UC1, MUC2, and MUC3 mRNA levels were present in adenomas and normal co lon, whereas mucin mRNA levels were decreased in adenocarcinomas. We c onclude that enhanced immunoreactivity of MUC1, MUC2 and MUC3 mucin ta ndem repeats occurs in adenomatous polyps and is associated with an in creased risk for malignant transformation.