The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status

Fondrevelle, Marie E.; Kantelip, Bernadette; Reiter, Robert E.; Chopin, Dominique K.; Thiery, Jean P.; Monnien, Franck; Bittard, Hugues; Wallerand, Hervé

doi:10.1016/j.urolonc.2007.12.012

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 27, Issue 3 , Pages 268-276, May 2009

The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status☆

Marie E. Fondrevelle, M.D.
- Department of Anatomy and Pathology, Centre Hospitalo-Universitaire Saint-Jacques, Besançon, France
Bernadette Kantelip, M.D., Ph.D.
- Department of Anatomy and Pathology, Centre Hospitalo-Universitaire Saint-Jacques, Besançon, France
Robert E. Reiter, M.D.
- Department of Urology, Jonsson Comprehensive Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
Dominique K. Chopin, M.D.
- Department of Urology, Centre Hospitalo-Universitaire Henri Mondor, Créteil, France
Jean P. Thiery, Ph.D.
- Institut Curie, UMR 144 CNRS (Centre Nationale de la Recherche Scientifique), Paris, France
Franck Monnien, Ph.D.
- Department of Anatomy and Pathology, Centre Hospitalo-Universitaire Saint-Jacques, Besançon, France
Hugues Bittard, M.D., Ph.D.
- Department of Urology, Centre Hospitalo-Universitaire Saint-Jacques, Besançon, France
Hervé Wallerand, M.D., Ph.D.
- Department of Urology, Centre Hospitalo-Universitaire Pellegrin-Tripode, Bordeaux, France
- Corresponding author. Tel.: +33 5 56 79 55 35; fax: +33 5 56 79 56 51

Received 17 October 2007; received in revised form 17 December 2007; accepted 17 December 2007. published online 28 April 2008.

Abstract

Objectives

Twist is considered as transcription factor that regulates epithelial mesenchymal transition (EMT) by at least inhibition of E-cadherin expression. EMT is a key event in the tumor invasion process. The purpose of this study is to investigate the expression of Twist but also those of E- and N-cadherin in human primary bladder tumor and to evaluate its prognostic value. As smoking cigarettes is a strong bladder cancer risk factor, we tried to evaluate the impact of the tobacco status on these molecular abnormalities.

Materials and Methods

To delineate on the oncogenic role for Twist in human bladder cancer, we evaluated the E- and N-cadherin but also Twist expression (n = 70) by immunohistochemistry. We evaluated the prognostic value of these expressions. Moreover, we tried to correlate these protein expressions to the smoking status of the patients. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis.

Results

Of the 70 bladder tumors, 28 (40%) cases were positive for Twist expression, 16 (23%) cases were negative for E-cadherin expression, and 12 (17%) were positive for N-cadherin expression. When categorized into negative vs. positive expression, Twist was associated with the stage (P = 0.001), the grade (P < 0.001), the progression (P = 0.02), and the E-cadherin expression (P = 0.01). Moreover, positive Twist expression clearly predicted poorer PFS (P = 0.02). In the multivariate analysis, both positive Twist expression and loss of E-cadherin expression were independent prognostic factors for PFS (P = 0.046 and P = 0.001, respectively) and only loss of E-cadherin expression for the OS (P < 0.001). We also demonstrated that almost 60% (16/28) of patients with Twist-positive expression were current smokers at the time of the diagnosis, corroborating the fact that smoking modulates the expression of EMT markers including Twist.

Conclusion

Positive Twist expression may be a useful prognostic marker for patients with bladder cancer. Its expression seems to be correlated to the tobacco status of the patients.

Keywords: Twist, E-cadherin, Immunohistochemistry, Bladder cancer, Smoking status, Survival