Vascular endothelial growth factor expression, vascular volume, and capillary permeability in human brain tumors

OBJECTIVE: Vascular endothelial growth factor (VEGF) is an endothelial cell -specific mitogen and a potent inducer of vascular permeability. In this st udy, we determined whether expression of VEGF is correlated with in vivo me asurements of the capillary permeability and vascular volume of primary hum an brain tumors. METHODS: Tumor samples (seven glioblastomas, one anaplastic astrocytoma, tw o low-grade astrocytomas, one pilocytic astrocytoma, and three primary cere bral lymphomas) were stereotactically obtained from 14 patients. A semiquan titative polymerase chain reaction was used to quantify the relative expres sion of VEGF messenger ribonucleic acid in the tumors. VEGF protein was dem onstrated in tissue sections by immunohistochemical techniques. A two-compa rtment dynamic computed tomographic method was used to quantitatively measu re the aforementioned parameters in the regions from which the biopsies wer e obtained. RESULTS: In glial tumors, there was significant correlation of VEGF messeng er ribonucleic acid levels with capillary permeability (P < 0.05) and vascu lar volume (P < 0.01). Although all primary cerebral lymphomas showed consi derable increases in capillary permeability and vascular volume, VEGF expre ssion was only slightly upregulated in these tumors. CONCLUSION: Our findings are consistent with the hypothesis that VEGF may b e responsible for endothelial cell proliferation and vascular permeability in glial tumors. This relationship has implications for clinical applicatio ns, i.e., assessment of delivery of water-soluble drugs, treatment of edema , and antiangiogenesis therapy based on inhibition of VEGF function.