Prognostic Role of Epithelial-Mesenchymal Transition Markers "E-Cadherin, β-Catenin, ZEB1, ZEB2 and p63" in Bladder Carcinoma

Background: This study aimed to investigate the expression of epithelial-mesenchymal markers' E-cadherin, beta-catenin, zinc-finger E-box-binding homeobox 1 (ZEB1), zinc-finger E-box-binding homeobox 2 (ZEB2) and p63 in transitional cell carcinoma (TCC) and squamous cell carcinoma (SCC) variants of bladder carcinoma (BC) and their correlation with clinicopathological parameters of prognostic importance. Methods: In this retrospective study, 91 patients were enrolled (66 with TCC and 25 with SCC). All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors. Results: In TCC cases, reduced E-cadherin, beta-catenin positivity and p63 expression rate were evident in the sitting of increased expression of ZEB1 and ZEB2. Patients with ZEB2 positive tumors were more likely to die compared to those with negative ZEB2 (P = 0.024). Moreover, in patients with muscle-invasive BCs, an intense p63 expression was associated with poor overall survival (OS) (P < 0.001). For patients with SCC, there was a reduction in E-cadherin and beta-catenin positivity with elevated p63 expression and concomitant increased ZEB1 and ZEB2 expression. Poor prognosis was evident in association with reduced E-cadherin, positive nuclear beta-catenin/reduced membranous beta-catenin, ZEB1 and ZEB2 positive cases as well patients with elevated p63 expression (P < 0.001). TCC and SCC cases showed similar poor prognosis in association with elevated p63 expression (P < 0.001). Conclusions: In both TCC and SCC variants, epithelial-mesenchymal transition (EMT) process is evident; however, its molecular mechanism shows some variations, specifically this notably different p63 expression pattern among two carcinoma variants with the similar impact of elevated p63 expression pattern on prognosis.