title: N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors.
abstract: OBJECTIVE
  Loss of intercellular adhesion and increased cell motility promote tumor cell invasion and spreading. In bladder cancer, loss or reduced E-cadherin expression has been associated with poor survival, and aberrant expression of N-cadherin has been associated with the invasive phenotype of bladder carcinoma cells. The purpose of this study was to investigate whether N-cadherin expression was associated with the bladder tumor progression.
  
  
  METHODS
  E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101 tumors (pT1 and pT2-T3) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pT(a), pT1, and pT2-T3).
  
  
  RESULTS
  N-cadherin expression was absent in normal urothelium, appeared in stage pT1, and increased in pT2-pT3 tumors. In most cases, increased N-cadherin expression in invasive tumors was associated with loss of E-cadherin expression. Progression-free survival and multivariate analyses revealed that N-cadherin expression is an independent prognostic marker for pT1 tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT1 and pT2-T3 tumors. Interestingly, in pT(a) tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases.
  
  
  CONCLUSIONS
  Regulatory defects in the N-cadherin promoter, abnormalities at the translational, or protein processing levels could explain the discrepancies between protein and mRNA expression. Most importantly, this study identified N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clearly, N-cadherin acts in an invasive mode in bladder cancer, but whether it has a primary role in urothelial neoplastic progression has yet to be investigated.
authors: Tissue and Cell Biology Engineering, Besançon, France. isabelle.lascombe@viola.fr
authors: Isabelle
authors: I
authors: Lascombe
authors: Anne
authors: A
authors: Clairotte
authors: Sylvie
authors: S
authors: Fauconnet
authors: Stéphane
authors: S
authors: Bernardini
authors: Hervé
authors: H
authors: Wallerand
authors: Bernadette
authors: B
authors: Kantelip
authors: Hugues
authors: H
authors: Bittard