Angiogenic factors in the cerebrospinal fluid of patients with astrocytic brain tumors.
OBJECTIVE
Gliomas account for most primary brain tumors in adults, and survival correlates with the grade and vascularity of the tumor. The degree of tumor-related angiogenesis seems to be a significant predictor of tumor progression, recurrence, and metastatic spread in a variety of malignant diseases, including brain tumors. Our study's objective was to quantify the levels of two angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), in the cerebrospinal fluid (CSF) and serum of patients with gliomas and to correlate these levels with tumor grade, vascularity, and overall survival.


METHODS
Twenty-six patients with the diagnosis of cerebral glioma (19 high-grade, 7 low-grade) comprised the study group. Ten patients with communicating hydrocephalus served as controls. Levels of VEGF and bFGF in the CSF and serum were determined using enzyme-linked immunosorbent assay analysis. Tumor vascularity was graded qualitatively using immunohistochemical staining for CD34. Nonparametric statistical techniques were used for data analysis.


RESULTS
Median levels of bFGF and VEGF in the CSF were significantly higher in patients with high-grade glioma as compared with patients with low-grade glioma or hydrocephalus (bFGF levels, 52, 26, and 24 ng/ml, respectively, P < 0.0001; VEGF levels, 17.6, 7.2, and 8.3 ng/ml, respectively, P < 0.005). A significant correlation was found comparing CSF levels of bFGF with levels of VEGF (P < 0.001). The levels of the angiogenic factors in the CSF correlated with the degree of tumor vascularity and were adversely associated with patient survival. Serum levels of the angiogenic factors showed no correlation to tumor grade, vascularity, or survival.


CONCLUSIONS
Our data suggest that CSF levels of bFGF and VEGF may serve as an additional marker for tumor grading and vascularity and may help predict survival.
Peles
Einat
E
Department of Neurosurgery, Sheba Medical Center, Tel-Hashomer and Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
Lidar
Zvi
Z
Simon
Amos J
AJ
Grossman
Rachel
R
Nass
Dvora
D
Ram
Zvi
Z
D043925:Angiogenesis Inducing Agents / Q000134:cerebrospinal fluid*; D001254:Astrocytoma / Q000098:blood supply* / Q000134:cerebrospinal fluid / Q000401:mortality; D001932:Brain Neoplasms / Q000098:blood supply* / Q000134:cerebrospinal fluid / Q000401:mortality; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000134:cerebrospinal fluid*; D005909:Glioblastoma / Q000098:blood supply* / Q000134:cerebrospinal fluid / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000134:cerebrospinal fluid* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D013223:Statistics as Topic; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000134:cerebrospinal fluid*
D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2