Epithelial-mesenchymal transition markers in metastatic transitional cell carcinoma (mTCC) patients under vinflunine treatment.

Abstract

e15532 Background: Vinflunine (VFL) demonstrated in vitro antiproliferative effects in human tumour cell lines, and in vitro antitumor activities against subcutaneous tumour xenografts. Recently, we demonstrated that VFL causes these effects through tubulin instability, which is one of the leading intracellular molecular process that drives epithelial-mesenchymal transition (EMT). In addition, VFL may induce up-regulation in expression levels of E-cadherin/N-cadherin cocient. Methods: The study included a retrospective analysis of 18 patients with mTCC treated with carboplatin-based chemotherapy. The patients who demonstrated objective response (38.8%) continued with vinflunine 320 mg/m2 one day every three weeks until progression. EMT protein expression (E-cadherin, beta-catenin, vimentin, CK18) was evaluated by Western blotting and also by immunohistochemistry (IHQ). Results: Overall mean age of patients was 71 years. The median overall survival was 3.5 years for the carboplatin-based chemotherapy (95% CI, 0.377-3.623). In patients treated with VFL, it was demonstrated a correlation of performance status and overall response with the histological type and age. We also found a relationship between different EMT markers in patients that received VFL. Conclusions: The above data provide evidence for an intrincate mechanism by which VFL could stop the transition from epithelial cells to the invasive mesenchymal phenotype. Molecular mechanism of Snail, Slug, Twist and Hakai will be reported.