title: Integrins αvβ6, α6β4 and α3β1 are down-regulated in cholangiolocellular carcinoma but not cholangiocarcinoma.
abstract: OBJECTIVE
  The aim of this study was to evaluate integrin expression and immunolocalization of the extracellular matrix proteins in cholangiolocellular carcinoma (CoCC).
  
  
  METHODS
  Tissue specimens of 23 CoCC, 28 cholangiocarcinomas (CCC), 42 hepatocellular carcinomas (HCC) and 11 classical type combined hepatocellular cholangiocarcinomas (CHC) were immunostained for β6, β4 and α3 integrins, fibronectin and laminin. ITGB6, B4 and A3 mRNA levels in six HCC cell lines, five CCC cell lines and two CHC cell lines were quantified by quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Little or no positivity for β6, β4 and α3 integrins was shown in 91%, 91% and 52% of CoCC and 100%, 98% and 81% of HCC, respectively, according to immunostaining, whereas intense positive staining for these integrins was demonstrated in 64%, 96% and 75% of CCC, respectively. There was a close correlation between β4 and α3 integrin expression and intracytoplasmic laminin in CoCC, CCC and HCC, but not between β6 expression and its ligand, fibronectin. Integrin mRNA levels were increased in four of five CCC cell lines, but nearly undetectable in five of six HCC cell lines and one CHC cell line. Tubular differentiation of a CHC cell line cultured in collagen gel matrix induced upregulation of these integrins.
  
  
  CONCLUSIONS
  Our results first indicated downregulation of αvβ6, α6β4 and α3β1 integrins in CoCC, in contrast to its high expression in CCC, suggesting a diagnostic value of integrins in the differential diagnosis of CoCC and CCC, as well as a useful inducible marker of the intermediate features of CoCC.
authors.affiliation: Department of Pathology, Teikyo University School of Medicine, Tokyo, Japan; 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.forename: Masafumi
authors.initials: M
authors.lastname: Inoue
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.forename: Motoji
authors.initials: M
authors.lastname: Sawabe
authors.forename: Toshio
authors.initials: T
authors.lastname: Fukusato
keywords: cholangiocarcinoma; cholangiolocellular carcinoma; hepatocellular carcinoma; integrin; laminin; stem cell features