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 study, we determined whether expression of VEGF is correlated with in vivo measurements of the capillary permeability and vascular volume of primary human brain tumors.


METHODS
Tumor samples (seven glioblastomas, one anaplastic astrocytoma, two low-grade astrocytomas, one pilocytic astrocytoma, and three primary cerebral lymphomas) were stereotactically obtained from 14 patients. A semiquantitative polymerase chain reaction was used to quantify the relative expression of VEGF messenger ribonucleic acid in the tumors. VEGF protein was demonstrated in tissue sections by immunohistochemical techniques. A two-compartment dynamic computed tomographic method was used to quantitatively measure the aforementioned parameters in the regions from which the biopsies were obtained.


RESULTS
In glial tumors, there was significant correlation of VEGF messenger ribonucleic acid levels with capillary permeability (P < 0.05) and vascular volume (P < 0.01). Although all primary cerebral lymphomas showed considerable increases in capillary permeability and vascular volume, VEGF expression was only slightly upregulated in these tumors.


CONCLUSIONS
Our findings are consistent with the hypothesis that VEGF may be responsible for endothelial cell proliferation and vascular permeability in glial tumors. This relationship has implications for clinical applications, i.e., assessment of delivery of water-soluble drugs, treatment of edema, and antiangiogenesis therapy based on inhibition of VEGF function.
Machein
M R
MR
Department of Neuropathology, University of Freiburg Medical School, Germany.
Kullmer
J
J
Fiebich
B L
BL
Plate
K H
KH
Warnke
P C
PC
D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000098:blood supply / Q000737:chemistry*; D002648:Child; D016228:Endothelial Growth Factors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009389:Neovascularization, Pathologic; D016133:Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors