Expression of mucin antigens in human cancers and its relationship with malignancy potential.

Mucins are high molecular weight glycoproteins having oligosaccharides attached to the apomucin protein backbone by O-glycosidic linkages. Biochemical studies on the structures and the organ specificities of several mucin core proteins (MUC1-MUC7) have been reported during the past several years. In the present study of pancreas and intrahepatic bile duct tumors, MUC1 mucin (membrane bound mucin detected by monoclonal antibody, DF3) was highly expressed in invasive ductal carcinomas of the pancreas (IDC) and invasive cholangiocarcinomas of the liver (ICC), which show invasive growth and a poor prognosis, but it was rarely expressed in intraductal papillary mucinous tumors of the pancreas (IPMT) and bile duct cystadenocarcinomas of the liver (BDCC), which show a favorable prognosis. In contrast, MUC2 mucin (intestinal type secretory mucin detected by polyclonal antibody, anti-MRP) was rarely expressed in IDC and ICC, whereas it was highly expressed in IPMT and BDCC. The results suggest that the differences in the expression of MUC1 and MUC2 mucins are a useful prognostic indicator of malignancy potential in the neoplasms of the pancreas and intrahepatic bile duct. Moreover, the expression of MUC1 and MUC2 mucins was a useful indicator of the malignancy potential of tumors derived from other organs, such as the ampulla of Vater, stomach and breast. In another study on the expression of several MUC1 mucin antigens with different patterns of glycosylation, sialylated-MUC1 mucin detected by monoclonal antibody, MY.1E12, was found to be expressed in all the invasive carcinomas (IDC and ICC) but was not frequently seen in the non-invasive type tumors (IPMT and BDCC), although the other types of MUC1 mucins did not show such contrast between the invasive and non-invasive type tumors. The results suggest that sialylation of MUC1 mucin is associated with invasive growth of neoplasms. In contrast, our study of the expression of MUC2 mRNA (transcript of intestinal type mucin) and MUC5AC mRNA (transcript of gastric type mucin) by in situ hybridization in the tumors of the pancreas and intrahepatic bile duct found that the non-invasive type tumors (IPMT and BDCC) synthesize MUC2 mRNA and MUC5AC mRNA, whereas most of the invasive carcinomas (IDC and ICC) do not. Furthermore, patients positive for MUC2 mRNA or MUC5AC mRNA expression in the tumors showed significantly better survival than the patients with no expression. The production of MUC2 or MUC5AC, an abundant extracellular intestinal or gastric type secretory mucin with high viscosity may be correlated, by a majority of the non-invasive type tumors, with the expansive growth of the tumors that display lower levels of invasion and metastasis.