Abstract 1590: N-cadherin is a key marker for epithelial-to-mesenchymal transition in clinical prostate cancer

Abstract

Abstract Purpose of the study: Epithelial-to-mesenchymal transition (EMT) is characterized by E cadherin downregulation and simultaneous upregulation of mesenchymal markers such as vimentin, fibronectin and N cadherin. Studies on EMT are generally performed in cell lines and mouse models, while the histopathological and phenotypical properties in clinical prostate cancer (PCa) are still unclear. Our objective was to analyze the expression of various EMT markers in clinical PCa samples. Experimental procedures: We performed immunofluorescent double stainings with E cadherin and the mesenchymal markers N cadherin, vimentin or fibronectin, Zeb1, Twist1, and β catenin on fresh frozen radical prostatectomies. Summary: Immunofluorescent double stainings with E cadherin and the mesenchymal markers N cadherin, vimentin or fibronectin demonstrate that E cadherin was consistently downregulated in N cadherin positive PCa cells, but not vimentin or fibronectin positive PCa cells. Moreover, co expression of mesenchymal markers was uncommon, as PCa cells did not co express N-cadherin with fibronectin and only rarely (<1%) cells with vimentin. Membranous expression of β-catenin was unaltered in N cadherin positive PCa cells, while nuclear staining could not detected. Zeb1 was expressed in the nuclei of surrounding fibroblasts, but not in PCa cells. Twist1 was localized to the nucleus of some N-cadherin negative PCa cells, but not in N-cadherin positive cells. Conclusions: We demonstrated that N cadherin was the most reliable marker for EMT in clinical PCa as compared to vimentin and fibronectin, and that these mesenchymal markers were generally not expressed within the same cell population. The expression of N-cadherin was not associated with Twist1, Zeb1 or β-catenin expression. Despite extensive knowledge of EMT in PCa cell lines, the molecular mechanisms involved in EMT in clinical PCa is still unknown. Citation Format: Kimberley Kolijn, Esther I. Verhoef, Geert J.L.H. van Leenders. N-cadherin is a key marker for epithelial-to-mesenchymal transition in clinical prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1590.