Peritumoral brain edema in angiomatous supratentorial meningiomas: an investigation of the vascular endothelial growth factor A pathway

The aim of this work was to study the vascular endothelial growth factor A (VEGF-A) pathway and peritumoral brain edema (PTBE) through comparison of non-angiomatous and angiomatous meningiomas. Meningiomas are common intracranial tumors, which often have PTBE. VEGF-A is an integral part of PTBE formation and angiogenesis, and the capillary-rich angiomatous meningiomas are known for their PTBE. The VEGF-A receptor VEGFR-2 is responsible for the angiogenic effect of VEGF-A on endothelial cells, which is enhanced by the co-receptor neuropilin-1. Forty non-angiomatous, 22 angiomatous meningiomas, and 10 control tissue samples were collected for the study. Magnetic resonance images were available for 40 non-angiomatous and 10 angiomatous meningiomas. Tissue sections were immunostained for CD34, MIB-1, estrogen- and progesterone receptors. ELISA, chemiluminescence, and RT-qPCR were used for VEGF-A, VEGFR-2, and neuropilin-1 protein and mRNA quantification. Angiomatous meningiomas had larger PTBE (695 vs 218cm(3), p=0.0045) and longer capillary length (3614 vs 605mm/mm(3), p<0.0001). VEGF-A mRNA, neuropilin-1 mRNA, and VEGFR-2 protein levels were higher in angiomatous meningiomas independently of the capillary length (p<0.05). Neuropilin-1 protein levels were lower in angiomatous meningiomas (p<0.0001). The VEGF-A pathway and tumor capillary length may be essential for PTBE-formation in meningiomas. Further investigations of this pathway could lead to earlier therapy and targeted pharmacological treatment options.