Article first published online: 29 MAY 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 55, Issue 6, pages 1876–1888, June 2012
How to Cite
Komuta, M., Govaere, O., Vandecaveye, V., Akiba, J., Van Steenbergen, W., Verslype, C., Laleman, W., Pirenne, J., Aerts, R., Yano, H., Nevens, F., Topal, B. and Roskams, T. (2012), Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes. Hepatology, 55: 1876–1888. doi: 10.1002/hep.25595
Potential conflict of interest: Nothing to report.
Supported by an Interuniversity Attraction Pole (IUAP) grant from Belspo Belgium.
- Issue published online: 29 MAY 2012
- Article first published online: 29 MAY 2012
- Accepted manuscript online: 23 JAN 2012 06:11AM EST
- Manuscript Accepted: 23 DEC 2011
- Manuscript Received: 30 JUL 2011
- Interuniversity Attraction Pole (IUAP) grant from Belspo Belgium
Cholangiocellular carcinoma (CC) originates from topographically heterogeneous cholangiocytes. The cylindrical mucin-producing cholangiocytes are located in large bile ducts and the cuboidal non–mucin-producing cholangiocytes are located in ductules containing bipotential hepatic progenitor cells (HPCs). We investigated the clinicopathological and molecular features of 85 resected CCs (14 hilar CCs [so-called Klatskin tumor], 71 intrahepatic CCs [ICCs] including 20 cholangiolocellular carcinomas [CLCs], which are thought to originate from HPCs]) and compared these with the different cholangiocyte phenotypes, including HPCs. Immunohistochemistry was performed with biliary/HPC and hepatocytic markers. Gene expression profiling was performed in different tumors and compared with nonneoplastic different cholangiocyte phenotypes obtained by laser microdissection. Invasion and cell proliferation assay were assessed using different types of CC cell lines: KMC-1, KMCH-1, and KMCH-2. Among 51 ICCs, 31 (60.8%) contained only mucin-producing CC features (muc-ICCs), whereas 39.2% displayed histological diversity: focal hepatocytic differentiation and ductular areas (mixed-ICCs). Clinicopathologically, muc-ICCs and hilar CCs showed a predominantly (peri-)hilar location, smaller tumor size, and more lymphatic and perineural invasion compared with mixed-ICCs and CLCs (predominantly peripheral location, larger tumor size, and less lymphatic and perineural invasion). Immunoreactivity was similar in muc-ICCs and hilar CCs and in mixed-ICCs and CLCs. S100P and MUC1 were significantly up-regulated in hilar CCs and muc-ICCs compared with mixed-ICCs and CLCs, whereas NCAM1 and ALB tended to be up-regulated in mixed-ICCs and CLCs compared with other tumors. KMC-1 showed significantly higher invasiveness than KMCH-1 and KMCH-2. Conclusion: Muc-ICCs had a clinicopathological, immunohistochemical, and molecular profile similar to that of hilar CCs (from mucin-producing cholangiocytes), whereas mixed-ICCs had a profile similar to that of CLCs (thought to be of HPC origin), possibly reflecting their respective cells of origin. (HEPATOLOGY 2012;55:1876–1888)