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

Author(s)

Vasconcelos, Artur Cunha ^[1] ; Wagner, Vivian Petersen ^[1] ; Meurer, Luise ^[2] ; Vargas, Pablo Agustin ^[3] ; de Souza, Lelia Batista ^[4] ; Fonseca, Felipe Paiva ^[3] ; Squarize, Cristiane Helena ^[5] ; Castilho, Rogerio Moraes ^[5] ; Martins, Manoela Domingues ^[1]

Affiliation

^[1] Univ Fed Rio Grande do Sul, Sch Dent, Dept Oral Pathol, BR-90035003 Porto Alegre, RS - Brazil

^[2] Hosp Clin Porto Alegre HCPA UFRGS, Dept Pathol, Porto Alegre, RS - Brazil

^[3] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, Sao Paulo - Brazil

^[4] Univ Fed Rio Grande do Norte, Dept Oral Pathol, BR-59072970 Natal, RN - Brazil

^[5] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Lab Epithelial Biol, Ann Arbor, MI 48109 - USA

• Document type: Journal article
• Source: ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY; v. 120, n. 2, p. 238-247, AUG 2015.
• Web of Science Citations: 3

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. 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. (AU)

• FAPESP's process: 12/10781-7 - Analysis of the expression of cytokeratins, angiogenic and proliferative patterns, and DNA content of salivary gland tumors
• Grantee: Pablo Agustin Vargas
• Support Opportunities: Regular Research Grants