title: Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma.
abstract: OBJECTIVE
  Hepatocellular carcinomas (HCCs) commonly originate from pre-malignant lesions consisting of mature hepatocytes. However, recent studies have suggested that some HCCs emerge from hepatic stem/progenitor cells because stem/progenitor cell markers and cholangiocyte markers are found in these HCCs. At the same time, the expression of stem/progenitor cell markers and cholangiocyte markers may also indicate de-differentiation and transdifferentiation of ordinary HCC cells. This study was performed to help clarify the uncertainty surrounding these HCCs.
  
  
  METHODS
  Sixty-eight surgically resected HCC lesions no larger than 5 cm were studied immunohistochemically using a hepatocyte marker (Hepatocyte), 2 cholangiocyte markers (cytokeratins CK7 and CK19), a marker for mucin (Muc1), and a hepatic stem/progenitor cell marker (C-kit).
  
  
  RESULTS
  Hepatocyte, CK7, CK19, Muc1 and C-kit were positively stained in 68 cases (100%), 51 cases (75.0%), 15 cases (22.1%), 8 cases (11.8%) and 8 cases (11.8%), respectively. In those cases positive for CK7, CK19, Muc1 and C-kit, the positively stained cells formed small foci within a large area of negatively stained cells. Small-sized positive cells suggesting hepatic/stem cell origin were found rarely.
  
  
  CONCLUSIONS
  The positivity of cholangiocyte markers, the stem/progenitor cell marker and mucin production were thought to be due to transdifferentiation of HCC cells rather than malignant transformation of stem/progenitor cells.
authors.affiliation: Department of Surgery, Teikyo University, School of Medicine, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibuya
authors.forename: Fukuo
authors.initials: F
authors.lastname: Kondo
authors.forename: Keiji
authors.initials: K
authors.lastname: Sano
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Takada
authors.forename: Takehide
authors.initials: T
authors.lastname: Asano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D018450:Disease Progression; D005260:Female; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D053539:Keratin-19 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012189:Retrospective Studies; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D053552:Keratin-7; D018396:Mucin-1; D019009:Proto-Oncogene Proteins c-kit