Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors

• Published in: Oral surgery, oral medicine, oral pathology and oral radiology oral medicine, oral pathology and oral radiology, 2015-08, Vol.120 (2), p.238-247
• Main Authors: Vasconcelos, Artur Cunha, DDS, PhD, Wagner, Vivian Petersen, DDS, Meurer, Luise, MD, PhD, Vargas, Pablo Agustin, DDS, PhD, de Souza, Lélia Batista, DDS, PhD, Fonseca, Felipe Paiva, DDS, MS, Squarize, Cristiane Helena, DDS, PhD, Castilho, Rogerio Moraes, DDS, PhD, Martins, Manoela Domingues, DDS, PhD
• Format: Article
• Language: English
• Subjects: Adenoma, Pleomorphic - immunology; Biomarkers, Tumor - immunology; Carcinoma, Adenoid Cystic - immunology; Carcinoma, Mucoepidermoid - immunology; Dentistry; Hepatocyte Growth Factor - immunology; Humans; Immunohistochemistry; Microarray Analysis; Phosphatidylinositol 3-Kinases - immunology; Phosphorylation; Receptor Protein-Tyrosine Kinases - immunology; Salivary Gland Neoplasms - immunology; Signal Transduction; Surgery
• ISSN: 2212-4403; 2212-4411
• DOI: 10.1016/j.oooo.2015.04.003

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. Study Design 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.