Aberrant expression of MUC5AC and MUC6 gastric mucin genes in colorectal polyps

Altered mucin glycosylation and the de novo appearance of gastric mucin ant igens have been described in colonic adenomas. The purpose of our study was to determine if expression of the gastric mucin genes MUC5AC and MUC6 occu rs in colorectal adenomas and whether this correlates with histopathologic criteria of malignant potential. Immunohistochemical staining using antibod ies against MUC5AC and MUC6 tandem repeat synthetic peptides was performed on specimens of normal colon mucosa (n = 26), hyperplastic polyps (n = 9) a nd adenomatous polyps (n = 111). Mucin mRNA levels were determined using RN ase protection assays using riboprobes corresponding to unique non-repetiti ve sequences. MUC5AC and MUC6 staining were rarely detected and of low inte nsity in normal colon and hyperplastic polyps. The number of immunoreactive polyps and intensity of MUC5AC and MUC6 staining were greatest in larger a denomas of moderate villous histology and dysplasia. MUC5AC and MUC6 staini ng tended to decrease in highly villous polyps with severe dysplasia. Incre ased MUC5AC mRNA levels were found in 26/45 of adenomas tested compared wit h 0/9 normal colon specimens. MUC6 mRNA levels were found in 20/45 of adeno mas compared with 1/9 normal colon specimens. MUC5AC and MUC6 mRNA were pre sent more frequently and at higher levels in polyps with intermediate stage s of size, villous histology and dysplasia. We conclude that aberrant expre ssion of MUC5AC and MUC6 mucin genes is likely responsible for an expanded repertoire of mucin antigen expression in colorectal neoplasia. Published 1 999 Wiley-Liss, Inc.dagger