title: Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors.
abstract: OBJECTIVE
  The aim of this study was to analyze the expression pattern of proteins in the HGF/c-MET/PI3K signaling pathway in salivary gland tumors (SGTs) and to correlate the findings with the proliferative index and clinical parameters.
  
  
  METHODS
  We assembled tissue microarrays (TMAs) of 108 cases of SGTs, including 69 cases of pleomorphic adenoma (PA), 24 cases of adenoid cystic carcinoma (AdCC), and 15 cases of mucoepidermoid carcinoma (MEC). An immunohistochemical analysis of hepatocyte growth factor (HGF), MET phosphorylation (p-MET), protein kinase B (AKT) phosphorylation (p-AKT), and Ki-67 proteins was performed.
  
  
  RESULTS
  Benign and malignant SGTs presented similar scores of HGF-positive cells (P = .36), whereas, malignant SGTs exhibited higher levels of p-MET (P = .001) and p-AKT (P = .001) than benign SGTs. No correlation of HGF, p-MET, or p-AKT expression was observed with clinical parameters. PA had a lower proliferative index than either AdCC (P = .001) or MEC (P = .001).
  
  
  CONCLUSIONS
  The salivary gland carcinomas exhibited increased activation of the HGF pathway, as evidenced by the phosphorylation of the MET receptor, and increased activation of the PI3K pathway, as indicated by p-AKT. These data suggest that the HGF/c-MET/PI3K signaling pathway is active in SGTs, especially in malignant neoplasms.
authors.affiliation: Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Artur Cunha
authors.initials: AC
authors.lastname: Vasconcelos
authors.affiliation: Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Vivian Petersen
authors.initials: VP
authors.lastname: Wagner
authors.affiliation: Department of Pathology, Hospital de Clínicas de Porto Alegre (HCPA/UFRGS), Porto Alegre, Rio Grande do Sul, RS, Brazil.
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.affiliation: Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Pablo Agustin
authors.initials: PA
authors.lastname: Vargas
authors.affiliation: Department of Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors.forename: Lélia Batista
authors.initials: LB
authors.lastname: de Souza
authors.affiliation: Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, São Paulo, Brazil.
authors.forename: Felipe Paiva
authors.initials: FP
authors.lastname: Fonseca
authors.affiliation: Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
authors.forename: Cristiane Helena
authors.initials: CH
authors.lastname: Squarize
authors.affiliation: Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
authors.forename: Rogerio Moraes
authors.initials: RM
authors.lastname: Castilho
authors.affiliation: Department of Oral Pathology, School of Dentistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. Electronic address: manomartins@gmail.com.
authors.forename: Manoela Domingues
authors.initials: MD
authors.lastname: Martins
mesh_terms: D008949:Adenoma, Pleomorphic / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology; D003528:Carcinoma, Adenoid Cystic / Q000276:immunology*; D018277:Carcinoma, Mucoepidermoid / Q000276:immunology*; D017228:Hepatocyte Growth Factor / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology*; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D012468:Salivary Gland Neoplasms / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases