COLONIC EXPRESSION OF MUC2 AND MUC5AC IN INFLAMMATORY BOWEL DISEASE

Abstract

115 The product of the MUC2 mucin gene is the major colonic mucin in health and inflammatory bowel disease. MUC5AC, the major gastric mucin, is not normally expressed in the post partum colon but is produced by colonic adenocarcinoma-drived cell lines and is seen in mucus-producing colonic and extraintestinal neoplasms. Our aim in this study was to use specific antibodies to the MUC2 and MUC5AC mucins to characterize their distribution in colonic tissue sections from patients with inflammatory bowel disease. Methods: Paraffin sections from IBD patients and age matched normal controls were obtained from our histology library. Antibodies against the tandem repeat of MUC2 and the deglycosylated MUC5AC were used to localize the specific antigens by an indirect immunoperoxidase method. Results: In the normal colon MUC2 mucin was found only in goblet cells. In addition to this localization, the MUC2 antibody also stained surface epithelial cells in areas of colonic goblet cell depletion, principally in UC, but also in Crohn's colitis. These areas were rarely stained by the MUC5AC antibody, but MUC5AC was seen, co-expressing with MUC2, in goblet cells scattered throughout inflammed mucosa from UC, Crohn's, self limited colitis and solitary rectal ulcer. MUC5AC was also strongly expressed in areas of evident gastric metaplasia. Conclusions: These results show that colonic enterocytes are capable of producing MUC2 in areas of goblet cell depletion. These cells could represent goblet cell precursors appearing as part of post inflammatory regeneration or hyperstimulated goblet cells that no longer accumulate mucin granules. In either case loss of the goblet cell phenotype is not synonymous with loss of MUC2 expression. It is unlikely that these cells are undergoing dysplastic transformation since most of these cells do not seem to contain MUC5AC, as do dysplastic cells in other inflammatory areas. MUC5AC expression in colonic goblet cells appears to be an early and non-specific response to inflammation but could represent a very early marker of gastric metaplasia.