Snail Is an Independent Prognostic Indicator for Predicting Recurrence and Progression in Non-Muscle Invasive Bladder Cancer

Abstract

Background: Snail, an inducer of the epithelial-to-mesenchymal transition (EMT) increases motility and invasiveness of cancer cells by repressing E-cadherin expression. We investigate the relationship between Snail expression and clinicopathological parameters, and evaluate its prognostic significance in patients with non-muscle invasive bladder cancer (NMIBC). Methods: Three hundred thirty-two patients treated with transurethral resection of the bladder tumor (TURBT) between October 2002 and July 2010 were histopathologically confirmed to be NMIBC. Tumor recurrence and progression were followed up in all patients. Immunohistochemical staining of 332 slices was performed. The expression of Snail was evaluated by IHC and graded for intensity and area of staining. We correlated Snail scores with clinical and pathological variables, and association of Snail staining with tumor recurrence and progression was evaluated by univariate, multivariate analysis and Kaplan-Meier survival curves. Results: Of 332 patients with NMIBC, there was Snail positivity in 104 tumors (31.3%), and Snail expression correlated with age, multifocality, carcinoma in situ (CIS), tumor stage and tumor grade (each P < 0.05, respectively). A multivariate Cox regression model revealed that Snail expression was an independent predictor of tumor recurrence (hazard ratio (HR): 1.95, P = 0.001) and progression (HR: 2.34, P = 0.014) in patients with NMIBC. Kaplan-Meier estimates showed Snail expression was significantly associated with recurrence and progression (log-rank test, P < 0.0001, respectively). Conclusions: Analysis of Snail expression in 332 NMIBC tissue specimens revealed its potential usefulness as a biomarker to predict the NMIBC prognosis.