Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer.

Abstract

Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas. The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient's prognosis. The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer's exact test and Spearman's test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test. A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p=0.024), loco-regional recurrences (p=0.028), and lymph node metastasis (pN+) (p=0.010) was found. The membranous (p=0.000 and r=0.384) and cytoplasmic (p=0.000 and r=0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p=0.006 and r=0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip. Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion. Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.