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.