Epithelial-to-Mesenchymal Transition and Neoangiogenesis in Laryngeal Squamous Cell Carcinoma.

Abstract

Simple summaryThe mechanism of epithelial–mesenchymal transition is fundamental for carcinogenesis, tumor progression, cancer cell invasion, metastasis, recurrence, and therapy resistance, resulting in cellular junction degradation and increased cellular motility. The same factors that drive epithelial cells toward a mesenchymal phenotype may also drive endothelial cells toward a proangiogenic phenotype. This study aimed to investigate a potential interplay between epithelial–mesenchymal transition and angiogenesis in laryngeal carcinoma. In our study, univariate Cox regression identified pN+ status and Slug expression as predictive of disease-free survival, while a trend toward significance emerged for CD105-assessed microvessel density and N-cadherin expression. In the multivariate Cox regression model, pN-status, Slug, and N-cadherin expressions retained their significant values in predicting disease-free survival. Data from our study support the hypothesis of a mutual concurrence of epithelial–mesenchymal transition and angiogenesis in the development of an aggressive phenotype in laryngeal squamous cell carcinoma.The mechanism of epithelial–mesenchymal transition (EMT) is fundamental for carcinogenesis, tumor progression, cancer cell invasion, metastasis, recurrence, and therapy resistance, comprising important events, such as cellular junction degradation, downregulation of epithelial phenotype markers, overexpression of mesenchymal markers, and increase in cellular motility. The same factors that drive epithelial cells toward a mesenchymal phenotype may also drive endothelial cells toward a proangiogenic phenotype. The aim of this exploratory study was to investigate a potential interplay between EMT and angiogenesis (quantified through CD105 expression) in laryngeal carcinoma (LSCC). CD105-assessed microvessel density (MVD) and EMT markers (E-cadherin, N-cadherin, Snail, Slug, Zeb1, and Zeb2) were assessed on 37 consecutive LSCC cases. The univariate Cox regression model identified pN+ status (p = 0.0343) and Slug expression (p = 0.0268) as predictive of disease-free survival (DFS). A trend toward significance emerged for CD105-assessed MVD (p = 0.0869) and N-cadherin expression (p = 0.0911). In the multivariate Cox model, pN-status, Slug, and N-cadherin expressions retained their significant values in predicting DFS (p = 0.0346, p = 0.0430, and p = 0.0214, respectively). Our data support the hypothesis of a mutual concurrence of EMT and angiogenesis in driving LSCC cells toward an aggressive phenotype. To better characterize the predictive performance of prognostic models based on EMT and angiogenesis, further large-scale prospective studies are required.