title: Intrahepatic cholangiocarcinoma arising in cirrhotic liver frequently expressed p63-positive basal/stem-cell phenotype.
abstract: In general, intrahepatic cholangiocarcinoma (ICC) is not related to liver cirrhosis. However, a few cases have been reported in which ICC was accompanied by severe liver fibrosis. Some researchers have proposed that hepatocellular and cholangiocellular (HC-CC) carcinoma, an intermediate mixed phenotype possibly arising in cirrhotic liver, might originate from hepatic precursor cells. In the liver, hepatocytes and cholangiocytes form the epithelial element, but stromal and mesenchymal elements may be produced by hepatic stem cells. Based on these aspects, not only HC-CC, but also other combinations of cellular phenotypes, would cover all the cancers with stem cell features. In this study, which aimed at determining the characteristics of the ICC phenotype, we used immunohistochemistry to examine the expression of basal/stem-cell markers, i.e., p63 in ICC with and without liver cirrhosis, as well as the expressions of cytokeratin (CK) 34 beta E12, specific for the basal-cell marker, and c-kit, specific for the stem-cell marker. Aberrant p63 was frequently expressed in ICC arising in cirrhotic liver. This result suggests that ICC cancer cells originate from hepatic precursor cells with a hidden multi-differentiation potential.
authors.affiliation: Department of Pathology I, Faculty of Medicine, Toyama University, 2630 Sugitani, Toyama-City, Toyama 930-0194, Japan. kazunomoto@syd.odn.ne.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Tsuneyama
authors.forename: Chunmei
authors.initials: C
authors.lastname: Cheng
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hori
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Murai
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Takano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000209:etiology / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation; D018281:Cholangiocarcinoma / Q000209:etiology / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D053552:Keratin-7; D007633:Keratins / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D013234:Stem Cells / Q000737:chemistry; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C507497:KRT7 protein, human; D053552:Keratin-7; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D007633:Keratins; D019009:Proto-Oncogene Proteins c-kit