Role of VEGF and matrix metalloproteinase-9 in peritumoral brain edema associated with supratentorial benign meningiomas

Accumulating evidence indicates that VEGF and matrix metalloproteinase-9 (MMP-9) play a central role in the development of peritumoral brain edema (PTBE) associated with human brain tumors. However, the roles of these proteins, particularly of MMP-9, in PTBE associated with benign meningiomas have not been elucidated. We investigated the association between clinical features and biological factors, such as VEGF and MMP-9, and the incidence of PTBE and edema index (EI) in 60 patients with benign meningiomas. In this study, supratentorial lesions were examined for evaluating the extent of PTBE in the surrounding normal brain tissue. VEGF and MMP-9 expression was immunohistochemically examined. Multivariate analysis revealed that the presence of pial blood supply (odds ratio [OR] 12.250; P=0.0096) and VEGF (OR 7.683; P=0.0155), but not MMP-9 (OR 1.178; P=0.8113), expression are significant factors that independently predict the incidence of PTBE and influence EI. VEGF (P=0.0397) and MMP-9 (P=0.0057) expression correlates with the presence of pial blood supply. Moreover, tumors with high VEGF and MMP-9 expression had higher EIs than those with high expression of either (P=0.030). Our findings suggest that MMP-9 expression was positively related to VEGF expression and pial blood supply and promoted the occurrence of PTBE by inducing the disruption of the arachnoid membrane and formation of pial blood supply.