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N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial Tumors

Authors' Affiliations: ¹ Tissue and Cell Biology Engineering; ² Faculty of Medicine and Pharmacy, University of Franche-Comte; ³ Urology and Andrology Department, St. Jacques University Hospital; ⁴ Pathologic Cytology and Anatomy Department, Jean Minjoz University Hospital, Besançon, France

Requests for reprints: Isabelle Lascombe, Tissue and Cell Biology Engineering, IFR 133, 240 route de Dole, 25000 Besançon, France. Phone: 33-3-63-08-22-28; E-mail: isabelle.lascombe{at}voila.fr.

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 (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.

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.

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