title: Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisola, 9-75, Bauru, SP, 17012-901, Brazil.
authors.forename: Agnes
authors.initials: A
authors.lastname: Assao
authors.affiliation: Adolfo Lutz Institute, Pathology Division, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 - 010, Brazil.
authors.forename: Suely
authors.initials: S
authors.lastname: Nonogaki
authors.affiliation: Department of Community Dentistry, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisola, 9-75, Bauru, SP, 17012-901, Brazil.
authors.forename: José Roberto Pereira
authors.initials: JRP
authors.lastname: Lauris
authors.affiliation: Fundação Pio XII Institution - Cancer Hospital of Barretos, R. Antenor Duarte Viléla, 1331, Barretos, SP, 14784-400, Brazil.
authors.forename: André Lopes
authors.initials: AL
authors.lastname: Carvalho
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Hospital, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 - 010, Brazil.
authors.forename: Clóvis Antônio Lopes
authors.initials: CAL
authors.lastname: Pinto
authors.affiliation: Department of Pathology, A.C. Camargo Cancer Hospital, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 - 010, Brazil.
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, Cancer Hospital A.C. Camargo, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 - 010, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisola, 9-75, Bauru, SP, 17012-901, Brazil. denisetostes@usp.br.
authors.forename: Denise Tostes
authors.initials: DT
authors.lastname: Oliveira
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008048:Lip Neoplasms / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D012307:Risk Factors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*; D000099149:Ezrin; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; D008562:Membrane Glycoproteins; D020742:rhoA GTP-Binding Protein; D000099149:Ezrin; C117468:PDPN protein, human; D000098853:Podoplanin
keywords: Ezrin; Oral cancer; Podoplanin; Rho-A