Vascular endothelial growth factor (
VEGF), a key regulatory
protein in neoangiogenesis, is strongly expressed in a variety of
primary brain tumors, particularly
malignant gliomas. In previous studies, high levels of
VEGF were also reported in
tumor cysts of
glioblastomas. Using an ELISA method we measured the concentration of
VEGF in matched samples of aspiration fluid from
tumor cysts and serum. Samples were collected from 14 patients with
primary brain tumors of various histology (six
glioblastomas, one protoplasmatic
astrocytoma, two
pilocytic astrocytomas, one
ependymoma, one
meningioma, and three
craniopharyngiomas) and two patients with solitary cystic
brain metastases from
adenocarcinomas of the lung. Aspiration fluids of
tumor cysts from all patients revealed high
VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2 to more than 2,000 times higher than the corresponding serum levels. Maximum
VEGF levels were detectable in cyst fluids from recurrent
glioblastoma. Serum
VEGF levels ranged between 125 and 716 pg/ml and did not differ from serum levels in 145 healthy volunteers. In a single patient with metastatic
lung cancer the concentration of
VEGF in serum and cyst fluid was determined during
disease progression. During 60 days of follow-up
VEGF concentrations in the cyst fluid collected by
puncture of an Ommaya reservoir increased 650-fold, while serum levels remained rather constant. These findings indicate that immunoreactive
VEGF is produced at the
tumor site and abundantly released into the cyst fluid of primary and metastatic
brain tumors. Interestingly, this abundant local release is not reflected in serum
VEGF levels, even in the case of very high
VEGF concentrations in
tumor cysts. Thus,
VEGF may be biologically relevant for the formation of
tumor cysts in
brain tumors and correlates with local
disease progression.