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

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 101tumors (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.

A‐FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells

“…Inversely, in poorly differentiated T24 cells, E-cadherin is absent and replaced by N-cadherin. 20 On the other hand, coregulator proteins can dramatically influence the activity of nuclear receptors and other transcription factors, thereby influencing cell fate. 38 RT4 cells could be deficient for a specific PPARa and g coactivator or characterized by the overexpression of a corepressor protein.…”

“…We chose as reference a non-invasive low-grade pTa tumor expressing the epithelial marker E-cadherin but not the mesenchymal marker Ncadherin. 19,20 The A-FABP mRNA level detected in this tumor was used as reference and set at 100% relative expression. Of 9 pTa tumors, 6 cases (66.6%) presented a high A-FABP expression.…”

Effects of dietary flavonoids, luteolin, and quercetin on the reversal of epithelial–mesenchymal transition in A431 epidermal cancer cells

“…(12,13) This phenomenon is correlated with the acquisition of invasiveness and metastatic potential by the cancer cells. Cadherin switching has been observed in biopsies from a wide range of types of cancers, including melanoma, breast, and prostate cancers, (12) bladder carcinoma, (14) some types of ovarian (15) and gastric carcinomas, (16,17) and adrenal tumors. (18) N-cadherin promotes tumor cell survival, migration, and invasion, and high level expression is often associated with a poor prognosis.…”

Diagnostic and Clinical Utility of Immunohistochemistry in Papillary Thyroid Carcinoma

“…(17)(18)(19) From the aforementioned results it could be suggested that immunostaining of N-Cadherin may play an important role in the diagnosis and prediction of the biological behavior of different histopathological types of PTC. In addition it can potentially be used for differential diagnosis between PTC and MNG and for prediction of synchronous metastatic existence.…”