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

Abstract

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, β-catenin, γ-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. r 2015 Elsevier Inc. All rights reserved.