Volume 44, Issue 2, Pages 350-358 (February 2006) Different expression patterns of mucin core proteins and cytokeratins during intrahepatic cholangiocarcinogenesis from biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct—an immunohistochemical study of 110 cases of hepatolithiasis  Yoh Zen, Motoko Sasaki, Takahiko Fujii, Tse-Ching Chen, Miin-Fu Chen, Ta-Sen Yeh, Yi-Yin Jan, Shiu-Feng Huang, Yuji Nimura, Yasuni Nakanuma  Journal of Hepatology  Volume 44, Issue 2, Pages 350-358 (February 2006) DOI: 10.1016/j.jhep.2005.09.025 Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 1 MUC1, MUC2, and MUC5AC expression in non-neoplastic and neoplastic biliary epithelial lesions. MUC1 expression is frequently observed in intrahepatic cholangiocarcinoma (ICC), especially ICC with biliary intraepithelial neoplasm (BilIN), compared to non-neoplastic and non-invasive lesions. MUC2 is expressed in most cases of intraductal papillary neoplasm of the bile duct (IPN-B). MUC5AC expression is observed in most cases of BilIN and IPN-B. *, P<0.001 in ICC with BilIN vs. BilINs, ICC with IPN-B vs. IPN-Bs, and ICC with IPN-B vs. ICC with BilIN; †, P<0.001 in IPN-B lineage (IPN-Bs and ICC with IPN-B) vs. non-neoplastic epithelium or BilIN lineage (BilINs and ICC with BilIN); ‡, P<0.001 in BilIN lineage or IPN-B lineage vs. non-neoplastic epithelium. Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 2 MUC1, MUC2, MUC5AC, CK7, and CK20 expression in a case of biliary intraepithelial neoplasia (BilIN-2). BilIN-2 is observed on the epithelium of the intrahepatic large bile ducts with intra-epithelial extension into peribiliary glands (glandular involvement: arrow) (HE). MUC1 (arrows), MUC5AC, and CK7 are expressed in tumor cells, whereas MUC2 and CK20 are not. (Original magnification ×100). Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 3 MUC1, MUC2, MUC5AC, CK7, and CK20 expression in a case of intraductal papillary neoplasm of the bile duct (IPN-B2). IPN-B2 shows prominent papillary proliferation with mucin hypersecretion (HE). MUC2, MUC5AC, CK7 (arrow), and CK20 (arrows) are expressed in tumor cells, whereas MUC1 is not. (Original magnification ×100). Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 4 Expression patterns of MUC1/MUC2 in non-neoplastic and neoplastic biliary epithelial lesions. In the biliary intraepithelial neoplasm (BilIN) lineage, the most common immunophenotype changes from MUC1−/MUC2− to MUC1+/MUC2− with histological-grade progression. In the intraductal papillary neoplasm of the bile duct (IPN-B) lineage, MUC1−/MUC2+ is the most common pattern in IPN-B, and ICC with IPN-B cases can be divided into two major groups: MUC1+/MUC2+ or MUC1−/MUC2+. Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 5 MUC1 and MUC2 expression in ICC with biliary intraepithelial neoplasm (BilIN) or intraductal papillary neoplasm of the bile duct (IPN-B). (A) ICC with BilIN consists of a non-invasive lesion (arrow) and poorly differentiated tubular adenocarcinoma. (B) MUC1 is expressed in the invasive lesion, but not in the non-invasive lesion. (C) ICC with IPN-B consists of the intraductal papillary proliferation of tumor cells (arrows) and an invasive colloid carcinoma (*). (D) MUC2 is expressed in both non-invasive and invasive lesions. (A: HE staining, B: MUC1, C: HE staining, D: MUC2, original magnification ×100 [A,B] and ×40 [C,D]). Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 6 CK7 and CK20 expression in non-neoplastic and neoplastic biliary epithelial lesions. All the cases examined except one (low-grade intraductal papillary neoplasm of the bile duct [IPN-B1]) show CK7 expression. CK20 expression is more commonly observed in the IPN-B lineage. *, P<0.001 in the IPN-B lineage (IPN-Bs and ICC with IPN-B) vs. non-neoplastic epithelium or the biliary intraepithelial neoplasm (BilIN) lineage (BilINs and intrahepatic cholangiocarcinoma (ICC) with BilIN). Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 7 Expression patterns of CK7/CK20 in non-neoplastic and neoplastic biliary epithelial lesions. CK7+/CK20− is the most common pattern in non-neoplastic biliary epithelium and the biliary intraepithelial neoplasm (BilIN) lineage, whereas CK7+/CK20+ is the most common pattern in the intraductal papillary neoplasm of the bile duct (IPN-B) lineage. Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions

Fig. 8 Histopathology of a case of intraductal papillary neoplasm of the bile duct (IPN-B1) with a unique immunophenotype (MUC1−/MUC2+/MUC5AC−/CK7−/CK20+). (Original magnification ×100). Journal of Hepatology 2006 44, 350-358DOI: (10.1016/j.jhep.2005.09.025) Copyright © 2005 European Association for the Study of the Liver Terms and Conditions