title: Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation.
abstract: BACKGROUND
  The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression.
  
  
  METHODS
  Ninety-four HCC lesions no larger than 8 cm from 94 patients were immuno-histochemically studied using two hepatocyte markers (Hep par 1 and α-fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c-Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0-5.0 cm; S3, 5.0-8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined.
  
  
  RESULTS
  The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c-Kit).
  
  
  CONCLUSIONS
  Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Kumagai
authors.affiliation: Department of Pathology, Teikyo University Hospital, Tokyo, Japan.
authors.forename: Fukuo
authors.initials: F
authors.lastname: Kondo
authors.affiliation: Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Sano
authors.affiliation: Department of Diagnostic Pathology, JCHO Tokyo Shinjuku Medical Center, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Pathology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Digestive Surgery, Hepatopancreatobiliary Surgery Unit, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masaji
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Soejima
authors.affiliation: Department of Pathology, Teikyo University Hospital, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Teikyo University Hospital, Tokyo, Japan.
authors.forename: Takuo
authors.initials: T
authors.lastname: Tokairin
authors.affiliation: Department of Pathology, Teikyo University Hospital, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Pathology, Teikyo University Hospital, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sasajima
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7 / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D047368:Tumor Burden / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D053552:Keratin-7; D019009:Proto-Oncogene Proteins c-kit
keywords: Hepatocellular carcinoma; Immunohistochemistry; Progenitor cell; Stem cell; Transdifferentiation