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


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.


CONCLUSIONS
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.
Fondrevelle
Marie E
ME
Department of Anatomy and Pathology, Centre Hospitalo-Universitaire Saint-Jacques, Besançon, France.
Kantelip
Bernadette
B
Reiter
Robert E
RE
Chopin
Dominique K
DK
Thiery
Jean P
JP
Monnien
Franck
F
Bittard
Hugues
H
Wallerand
Hervé
H
D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking; D051879:Twist-Related Protein 1 / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D015820:Cadherins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1