N-Cadherin As A Novel Prognostic Marker Of Progression In Superficial Urothelial Tumors

Purpose: 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.Experimental Design: E-cadherin and N-cadherin expression was evaluated by immunohistochemistry in 101 tumors (pT(1) and pT(2)-T-3) and by reverse transcription-PCR analysis and immunohistochemistry in 28 other fresh frozen tumors (pT(a), pT(1), and pT(2)-T-3).Results: N-cadherin expression was absent in normal urothelium, appeared in stage pT(1), and increased in pT(2)-pT(3) 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 pT(1) tumor progression. Analysis of the 28 frozen tumors by immunohistochemistry and reverse transcription-PCR showed a good correlation between protein and gene expression in pT(1) and pT(2)-T-3 tumors. Interestingly, in pT(a) tumors, N-cadherin was not immunodetected, whereas mRNA was present in 50% of cases.Conclusion: 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.