restricted recognition process. (HEPATOLOGY 1996;23: MUC1 apomucin is a specific target tumor antigen rec-1313-1317.) ognized by cytotoxic T cells in a major histocompatibility complex (MHC) unrestricted fashion in patients with pancreatic and breast cancer. This T-cell-mediated im-
Mucin is composed of abundant carbohydrates and mune mechanism against MUC1 apomucin expressing apomucin (mucin core protein). Seven apomucins cells has not been evaluated in nonneoplastic immune-(MUC1-7) have been cloned and characterized. [1][2][3][4][5][6][7][8][9] Howmediated diseases. Therefore, we immunohistochemiever, little is known about the distribution of these cally surveyed the expression of MUC1 apomucin on apomucins and their significance in normal and abnorbiliary epithelial cells of small bile ducts in various hepamal hepatobiliary systems. [10][11][12] We showed that MUC1 tobiliary diseases, including primary biliary cirrhosis apomucin is frequently expressed in cholangiocarci-(PBC). MUC1 apomucin was detected using the monoclonal antibody DF3 and the streptavidin-biotin com-noma 11 as well as in developing biliary epithelial cells plex, in livers from 31 patients with PBC, 67 with chronic in fetal livers, 12 whereas such expression is absent in viral hepatitis (CH) with or without cirrhosis, 31 with normal young and adult liver. 11,12 We proposed that extrahepatic biliary obstruction (EBO), 30 with hepatoli-MUC1 apomucin is an ''oncofetal'' antigen in the biliary thiasis, and from 23 normal individuals. MUC1 apomucin system. 12 was infrequently and focally expressed in the biliary epi-During these studies, we found that the biliary epithelial cells of the small bile ducts in 3 of 23 normal thelial cells of small bile ducts, particularly those assolivers. In contrast, MUC1 apomucin was frequently and ciated with hepatitic bile duct injury, [13][14][15] express strongly expressed on the luminal surface of biliary epi-MUC1 apomucin. This bile duct lesion histologically thelial cells of small bile duct, in 22 of 31 patients with mimics the chronic nonsuppurative destructive cholan-PBC, and in 50 of 67 patients with CH. In particular, gitis (CNSDC) of primary biliary cirrhosis (PBC). [16][17][18][19][20] high levels of MUC1 apomucin were expressed in bile ducts showing chronic nonsuppurative destructive chol-Cytotoxic T lymphocytes (CTLs) are predominant angitis (CNSDC) in PBC and hepatitic duct injuries in around and within the biliary epithelial cell layer of CH. In EBO and hepatolithiasis, MUC1 apomucin was CNSDC, 21 some of which are cytotoxic. 21 Mixed B cells focally and weakly expressed in 29% and 30% of livers and activated T cells are also predominant around hepexamined, respectively. More MUC1 apomucin was exatitic bile duct injury. 15 Immune mechanisms, includpressed in PBC and CH than in EBO, hepatolithiasis, ing cytotoxic T cells and the expression of immune adand normal liver (P รต .01, respectively). Frequent and hesion molecules, have been proposed in bile duct high luminal expression of MUC1 apomucin on biliary injury in PBC as well as in chronic viral hepatitis epithelial cells in damaged small bile ducts in PBC and (CH). 14,15,22 The exact immunopathology of these bile CH may be related to T-cell-mediated immunologic duct lesions, however, remains controversial. mechanisms in these diseases, probably by an MHC-un-CTLs isolated from tumor-infiltrating lymphocytes recognize polymorphic epithelial mucin core polypeptides, including MUC1 apomucin, 23,24 which is prefer-Abbreviations: MUC, apomucin; CNSDC, chronic nonsuppurative destruc-entially expressed on epithelial tumors. CTLs recogniztive cholangitis; PBC, primary biliary cirrhosis; CTL, cytotoxic T lymphocytes; ing MUC1 apomucin are induced and activated in CH, chronic viral hepatitis; MHC, major histocompatibility complex; EBO, patients with pancreas and breast cancer as well as extrahepatic biliary obstruction.
in multiple myeloma. [23][24][25][26][27] That is, activated CTLs can From the Department of Pathology (II), Kanazawa University School of recognize and directly bind MUC1 apomucin as a target Medicine, Kanazawa, Japan.