Circulating angiogenic factor levels correlate with extent of disease and risk of recurrence in patients with soft tissue sarcoma.
BACKGROUND
Tumor angiogenesis, or new blood vessel formation, is regulated by a balance between pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and anti-angiogenic factors such as endostatin.


METHODS
To investigate this angiogenic balance in soft tissue sarcomas (STS), blood samples were collected from 76 STS patients and 15 healthy controls, and analyzed for VEGF, bFGF and endostatin using quantitative enzyme-linked immunosorbent assays (ELISA).


RESULTS
Forty-one patients (54%) had primary tumors, 20 (26%) had local recurrences and 15 (20%) had metastatic disease with or without local disease. Levels of all three angiogenic factors were highly variable in STS patients. Mean levels of VEGF and bFGF were 12 and 14 times higher, respectively, in patients compared with controls (P<0.0001). VEGF levels correlated with size of tumor, with the highest levels found in tumors >10 cm in size. Patients with metastases had endostatin levels 45% lower than patients without metastases (P=0.047). In 54 patients who underwent resection of primary disease or local recurrence, low pre-operative bFGF level was associated with a higher risk of subsequent recurrence (P=0.044).


CONCLUSIONS
STS secrete widely variable levels of angiogenic factors, and levels of specific factors may correlate with extent of disease, predict risk of recurrence and possibly guide the use of anti-angiogenic agents.
Sarcoma Disease Management Team, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
S S
SS
Yoon
N H
NH
Segal
A B
AB
Olshen
M F
MF
Brennan
S
S
Singer
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D043169:Endostatins / Q000032:analysis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012307:Risk Factors; D012509:Sarcoma / Q000098:blood supply* / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000098:blood supply* / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis* / Q000378:metabolism
D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2