N-Cadherin as a Novel Prognostic Marker of Progression in Superficial Urothelial Tumors
- 1 May 2006
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 12 (9), 2780-2787
- https://doi.org/10.1158/1078-0432.ccr-05-2387
Abstract
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 (pTa, 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 pTa 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.Keywords
This publication has 37 references indexed in Scilit:
- Expression of E-Cadherin and α-,β-,γ-Catenins in Patients With Bladder CancerAmerican Journal of Clinical Pathology, 2006
- N-Cadherin Expression and Epithelial-Mesenchymal Transition in Pancreatic CarcinomaClinical Cancer Research, 2004
- Neoexpression of N-cadherin in E-cadherin positive colon cancersInternational Journal of Cancer, 2004
- Cell adhesion and signalling by cadherins and Ig-CAMs in cancerNature Reviews Cancer, 2004
- ‘Superficial’ bladder cancer - time to uncouple pT1 tumours from pTa tumoursBJU International, 2002
- EXPRESSION OF E-, P-, N-CADHERINS AND CATENINS IN HUMAN BLADDER CARCINOMA CELL LINESJournal of Urology, 2000
- N-Cadherin Promotes Motility in Human Breast Cancer Cells Regardless of Their E-Cadherin ExpressionThe Journal of cell biology, 1999
- Multiple Cadherins Are Expressed in Human FibroblastsBiochemical and Biophysical Research Communications, 1997
- Reduced expression of E-cadherin is related to invasive disease and frequent recurrence in bladder cancerZeitschrift für Krebsforschung und Klinische Onkologie, 1995
- Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor roleCell, 1991