Analysis of plasma and tissue expression of matrix metalloproteinases 2 and 9 in patients with pituitary adenomas and its correlation with invasive tumor behavior

• Grant number: 14/10462-4
• Support type: Regular Research Grants
• Duration: May 01, 2015 - April 30, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal researcher: Marcello Delano Bronstein
• Grantee: Marcello Delano Bronstein
• Home Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Assoc. researchers: Andrea Glezer ; Ericka Barbosa Trarbach ; Raquel Soares Jallad

Abstract

Although pituitary tumors are usually benign, about 5-35% have invasive behavior, extending to local tissues, including the cavernous sinus, sphenoid sinus, orbit and clivus. The reasons for these differences are poorly understood and, to date, there is no effective marker capable of predicting the invasive behavior of pituitary tumors. Considering that the invasiveness is the major determinant of therapeutic efficacy and prognosis in these tumors, the prior recognition of an invasive lesion could allow changes in the strategy of surgery, radiotherapy and drug therapy postoperatively, and predict the propensity for tumor recurrence. The MMP-2 and -9 (type IV collagenases) and their inhibitors (TIMPs) are related to the degradation of the basement membrane, an event considered critical in the process of tumor invasion. The role of these proteins has been studied in several human tumors, and a positive correlation between the expression of MMPs-2 and -9, including their quantification in serum/plasma, and aggressiveness/malignancy was already demonstrated. However, studies evaluating the expression of MMP-2 and -9 in pituitary adenomas showed some conflicting results and did not evaluate serum /plasma levels of these proteins. Therefore, in an unprecedented way, this study aims to evaluate the relationship between plasma and tissue expression of MMP-2, MMP-9, TIMP-1, - 2, -3 and -4, their enzymatic activity, and degree of tumor invasion, intending to contribute to the identification of a biomarker able to predict the pituitary adenoma's propensity to an invasive behavior.Additionally, analysis of PTTG and AIP genes, previously correlated with the arising and invasive potential of pituitary tumors, and hotspot mutations in GNAS, will also be performed to better characterize these samples in relation to already known biomarkers of invasiveness. (AU)