title: The expression of arginase-1, keratin (K) 8 and K18 in combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell type.
abstract: OBJECTIVE
  The WHO classification describes that combined hepatocellular-cholangiocarcinoma, subtypes with stem-cell features, intermediate-cell subtype (CHC-INT) is composed of tumour cells with features intermediate between hepatocytes and cholangiocytes. However, we previously reported that CHC-INT showed a high positive rate of biliary markers, but the expression of hepatocyte paraffin (HepPar)-1 was low. In this study, we examined the expression of other hepatocyte markers, such as arginase-1 (Arg-1), keratin (K) 8 and K18 in CHC-INT in order to examine the utility of pathological diagnosis in CHC-INT.
  
  
  METHODS
  We performed immunohistochemistry (IHC) of Arg-1, K8 and K18 using 32 previously diagnosed as CHC-INT. Immunoreactivity was evaluated with grading from 0 to 4 according to the distribution area of positive cells. The obtained findings of Arg-1, K8 and K18 were compared with those of K7, K19 and HepPar-1.
  
  
  RESULTS
  Out of the 32 cases, 22 (68.8%) cases were positive for Arg-1. Twenty-five (78.1%) were positive for K8. The IHC scores of Arg-1 and K8 were significantly higher than those of HepPar-1, but significantly lower than those of K7 and K19. The K18 expression was widely observed in all cases (100%). The IHC score of Arg-1 and K8 in CHC-INT was intermediate between hepatocellular carcinoma and cholangiocarcinoma.
  
  
  CONCLUSIONS
  Arg-1 and K8 were good markers to identify intermediate cells between hepatocytes and cholangiocytes. These can be useful markers for pathological diagnosis of CHC-INT, which usually has wide histological diversities, in combination with other hepatocytic and/or cholangiocytic markers.
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.affiliation: Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakashima
authors.affiliation: Biostatistics Center, Kurume University, Kurume, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kusano
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Reiichiro
authors.initials: R
authors.lastname: Kondo
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Tanikawa
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Todoroki
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Umeno
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Sanada
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Rin
authors.initials: R
authors.lastname: Yamaguchi
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ogasawara
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
mesh_terms: D000368:Aged; D001119:Arginase / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D053538:Keratin-18 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D007633:Keratins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; C488421:KRT18 protein, human; C426203:KRT8 protein, human; D053538:Keratin-18; D053533:Keratin-8; D007633:Keratins; C574619:ARG1 protein, human; D001119:Arginase
keywords: IMMUNOHISTOCHEMISTRY; KERATIN; LIVER CANCER