Immunolocalization of basic fibroblast growth factor to the microvasculature of human brain tumors.
BACKGROUND
Microvascular proliferation, a prominent feature of tumors of the central nervous system, is a prime target for anti-cancer therapy.


METHODS
Because basic fibroblast growth factor (bFGF) plays a key role in the regulation of angiogenesis, surgical specimens from 52 human brain tumors were examined by immunocytochemical studies with a murine monoclonal antibody to bFGF. Sections from these tumors also were incubated with Ki-67 monoclonal antibody to measure the growth fraction.


RESULTS
Immunostaining for bFGF was observed in 45 of 52 (87%) neoplasms, reacting with 97% of the malignant brain tumors and 67% of benign tumors (P < 0.01). The nonreactive tumors were a medulloblastoma and 7 of 21 (33%) benign, noninvasive, slow-growing neoplasms (1 acoustic schwannoma, 3 meningiomas, 2 pituitary adenomas, and 1 cholesteatoma). The indices of proliferation (Ki-67 labeling) were lower for the 21 benign tumors (1.2 +/- 1.1%) than the 31 malignant tumors (10.3 +/- 10.5%; P < 0.001). The bFGF was immunolocalized in the tumor cell nuclei in 23 of 52 tumors (44%) and in the cytoplasm of 8 of 52 (15%) tumors. Immunostaining to bFGF was prominent in the microvascular endothelial compartment in 84% of the malignant tumors and only 52% of benign tumors (P < 0.01). Immunostaining was not present after preabsorption of the antibody with pure human recombinant bFGF.


CONCLUSIONS
The presence of bFGF predominantly within the tumor microvasculature indicates a cellular depot for this potent growth factor that mediates angiogenesis and tumorigenesis. These data support a role for bFGF in the transition from the benign to the malignant phenotype.
Brem
S
S
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec.
Tsanaclis
A M
AM
Gately
S
S
Gross
J L
JL
Herblin
W F
WF
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000098:blood supply* / Q000737:chemistry*; D002467:Cell Nucleus / Q000737:chemistry; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D005629:Frozen Sections; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008833:Microcirculation / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D014407:Tumor Cells, Cultured
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016222:Fibroblast Growth Factor 2