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Title: Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes
Authors: Komuta, MIna ×
Govaere, Olivier
Vandecaveye, Vincent
Akiba, Jun
Van Steenbergen, Werner
Verslype, Chris
Laleman, Wim
Pirenne, Jacques
Aerts, Raymond
Yano, Hirohisa
Nevens, Frederik
Topal, Baki
Roskams, Tania #
Issue Date: Jun-2012
Publisher: W.B. Saunders
Series Title: Hepatology vol:55 issue:6 pages:1876-1888
Article number: 10.1002/hep.25595
Abstract: 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)(thought to be originated 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 non-neoplastic 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), while 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-ICC and CLC, while 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 similar clinicopathological, immunohistochemical, and molecular profile to hilar CCs (from mucin-producing cholangiocytes), while mixed-ICCs had a similar profile to CLCs (thought to be of HPC origin), possibly reflecting their respective cells of origin. (HEPATOLOGY 2012.).
URI: 
ISSN: 0270-9139
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Abdominal Transplantation
Hepatology
Radiology
Translational MRI (+)
Translational Cell & Tissue Research
Biomedical Sciences Group
Laboratory of Nephrology
Abdominal Surgical Oncology
× corresponding author
# (joint) last author

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