Expression of MUC1 and MUC2 mucin antigens in intrahepatic bile duct tumors: Its relationship with a new morphological classification of cholangiocarcinoma

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Abstract
Our previous immunohistochemical study on intrahepatic bile duct tumors showed that invasive cholangiocarcinoma (ICC) with a poor outcome expressed MUC1 mucin but was negative for MUC2 mucin, whereas bile duct cystadenocarcinoma (BDCC) with a favorable outcome was MUC1 negative and MUC2 positive. In the present study, ICC was further subdivided into 2 subtypes: intraductal growth type and/or periductal infiltrating type (ICC-IP) and mass forming type (ICC-M). The survival of patients with BDCC or ICC-IP is significantly better than that of patients with ICC-M. We examined these subtypes (ICC-IP and ICC-M) and BDCC for their expression of MUC1 mucins of different glycoforms. ICC-M showed significantly higher MUC1 expression rates (90%, 95%, and 85% positive rates as measured with the DF3, MY.1E12, and MUC1-Glycoprotein antibodies, respectively) than BDCC and ICC-IP (14% and 33%, 58% and 58%, and 0% and 50% positive respectively, as measured by the same antibodies). In contrast, BDCC (86% positive) and ICC-IP (67% positive) showed significantly higher MUC2 expression rates than ICC-M (25% positive) as measured with the anti-MRP antibody. Thus, the immunohistochemical staining pattern of ICC-IP resembled the pattern of BDCC more than they resembled ICC-M. In general, MUC1 expression is associated with poor patient outcome, irrespective of the glycosylation status. In particular, high expression of more sialylated forms of MUC1 mucins was correlated with poor survival. In contrast, expression of non-sialylated MUC2 mucin is a favorable prognostic indicator. These results suggest that ICC-IP is a different entity from ICC-M. This reclassification may have value in determining prognosis and treatment method.

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