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

• Published in: Clinical oral investigations 2017-06, Vol.21 (5), p.1647-1657
• Main Authors: Assao, Agnes, Nonogaki, Suely, Lauris, José Roberto Pereira, Carvalho, André Lopes, Pinto, Clóvis Antônio Lopes, Soares, Fernando Augusto, Kowalski, Luiz Paulo, Oliveira, Denise Tostes
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - pathology; Cytoskeletal Proteins - metabolism; Dentistry; Ezrin; Female; Humans; Immunohistochemistry; Lip; Lip Neoplasms - pathology; Lymph; Lymph nodes; Male; Medical prognosis; Medicine; Membrane Glycoproteins - metabolism; Metastases; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness - pathology; Neoplasm Staging; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Original Article; Phosphorylation; Prognosis; Proteins; rhoA GTP-Binding Protein - metabolism; Risk Factors; Statistical analysis
• ISSN: 1432-6981; 1436-3771
• DOI: 10.1007/s00784-016-1956-3

Introduction 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. Objective 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. Material and methods 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. Results 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. Conclusions 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. Clinical relevance 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.