Expression profile of epithelial-mesenchymal transition markers in non-muscle-invasive urothelial carcinoma of the bladder: Correlation with intravesical recurrence following transurethral resection

Objectives: To evaluate the expression of molecular markers involved in epithelial-mesenchymal transition (EMT), a key process mediating the progression of malignant tumors, in non muscle-invasive urothelial carcinoma of the bladder (NMIUCB) to clarify the significance of these markers as predictors of intravesical recurrence in patients treated with transurethral resection (TUR). Materials and methods: Expression levels of 13 EMT markers, including E-cadherin, N-cadherin, beta-catenin, gamma-catenin, fibronectin, matrix metalloproteinase (MMP)-2, MMP-9, Slug, Snail, TWIST, vimentin, ZEB1, and ZEB2, in TUR specimens obtained from 161 consecutive patients with NMIUCB were measured by immunohistochemical staining. Results: Of these 13 markers, significant differences in the incidence of intravesical recurrence were noted according to expression levels of E-cadherin, N-cadherin, MMP-2, MMP-9, and TWIST. Univariate analysis also identified expression levels of E-cadherin, N-cadherin, MMP-2, MMP-9 and TWIST, in addition to the tumor size, pathological T category, and concomitant carcinoma in situ, as significant predictors of intravesical recurrence-free survival. Of these significant factors, expression levels of E-cadherin, MMP-9, and TWIST; tumor size; and concomitant carcinoma in situ appeared to be independently associated with intravesical recurrence-free survival on multivariate analysis. Furthermore, there were significant differences in recurrence-free survival according to positive numbers of these 5 independent risk factors (i.e., positive for 0 or 1 factor vs. positive for 2 factors vs. positive for 3 or more factors). Conclusions: Consideration of expression levels of EMT-associated markers in TUR specimens, in addition to conventional prognostic parameters, would contribute to the accurate prediction of intravesical recurrence following TUR for NMIUCB. (C) 2015 Elsevier Inc. All rights reserved.