Expression of MMP-2, MMP-9 and TIMP-2 in pituitary tumors and their relationship with cavernous sinus invasion

Abstract

Objective: To evaluate the expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) in pituitary tumors and investigate their correlation with circulating plasma proteins and cavernous sinus invasion. In addition, the Ki-67 index was also assessed. Methods: Seventy-four patients (37 females) with pituitary adenomas were included, with preoperative peripheral blood collected in 29 cases. Tumor samples were evaluated for MMP-2, MMP-9, TIMP-2 and Ki-67 expression by immunohistochemistry. Protein plasma was semi-quantitatively detected using a commercial membrane antibody array. Results: Sixteen patients presented tumors invading the cavernous sinus. MMP-2 and TIMP-2 were slightly increased in these tumors compared to the noninvasive group, but the difference was not statistically significant. MMP-9 and TIMP-2 plasma concentrations did not correlate with tumor protein expression and also did not differ between the two groups. MMP-2 was not detected in plasma in any case. No statistically significant difference was observed when different tumor subtypes were considered. A significant difference was observed in tumor size (3.4 cm (2.8–4.9) vs 1.9 cm (1.3–2.6); P < 0.001) and in the Ki-67 index (1.8% (0.3–2.5) vs 0.5% (0.2–1.0); P = 0.01) between the invasive and noninvasive groups. Conclusions: In this cohort, we found no significant correlation between tissue and plasma levels of MMP-2, MMP-9 and TIMP-2 and cavernous sinus invasion in pituitary tumors. Further investigation is needed to elucidate the potential role of these markers in the invasiveness of pituitary tumors.

Keywords

• pituitary tumors
• invasiveness
• matrix metalloproteinase-2
• matrix metalloproteinase-9
• tissue inhibitor of metalloproteinase-2