Fiche publication
Date publication
mai 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BITTARD Hugues
,
Mr MONNIEN Franck
Tous les auteurs :
Fondrevelle ME, Kantelip B, Reiter RE, Chopin DK, Thiery JP, Monnien F, Bittard H, Wallerand H
Lien Pubmed
Résumé
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.
Référence
Urol Oncol. 2009 May-Jun;27(3):268-76
