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 218 cm(3) , p = 0.0045) and longer capillary length (3614 vs 605 mm/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.