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

Abstract

BackgroundThis study aimed to investigate the expression of epithelial-mesenchymal markers’ E-cadherin, β-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.MethodsIn 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.ResultsIn TCC cases, reduced E-cadherin, β-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 β-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 β-catenin/reduced membranous β-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).ConclusionsIn 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.

ZEB2 facilitates peritoneal metastasis by regulating the invasiveness and tumorigenesis of cancer stem-like cells in high-grade serous ovarian cancers

“…From the perspective of translational application, ZEB2 has been reported as an adverse prognostic marker in some tumours, such as breast cancer [ 38 ], bladder carcinoma [ 39 ] and glioma [ 40 ]. We thus retrospectively analysed 98 HGSOC patients to clarify the relationship between ZEB expression and clinical outcome.…”

Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression

“…On the other hand, the role of epithelial-to-mesenchymal transition (EMT) in BlCa prognosis has been widely discussed [28]. It has been shown to be highly related to an aggressive tumor biology, culminating in poor clinical outcome both in NMIBC and MIBC, namely poorer survival, increased recurrences, propensity to metastasize, and inferior response to treatment [29][30][31][32][33]. Herein, we aimed to characterize the expression of a set of markers for defining both luminal and basal/squamous subtypes in a well characterized patient cohort of BlCa, looking for clinicopathological correlates and testing their potential for clinical application, both within MIBC and NMIBC cases.…”

The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1

“…41,42 These results are also consistent with other research that demonstrate a reduction in E-Cadherin expression following DMBA induction. 42,43 DMBA's impact on E-Cadherin, like that of ICAM-1, is mediated via NFkB activation 37,38 via the Ras-Raf-MEK-ERK pathway 39 thus causing E-Cadherin repression due to transcription factor TWIST expression. 44 DMBA can also activate aryl hydrocarbon receptors (AhR), promoting transcription of SNAI2 (Slug), 45 an E-Cadherin repressor protein.…”