Serum endostatin levels are elevated in patients with soft tissue sarcoma.
BACKGROUND
Solid tumors are angiogenesis dependent, and elevated levels of proangiogenic cytokines have been reported in a variety of histologies. Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII. Because antiangiogenic protein fragments may be generated by tumor-derived proteases, the authors sought to determine whether circulating levels of endostatin were elevated in patients with localized soft tissue sarcoma.


METHODS
The authors analyzed preoperative serum levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate using a competitive enzyme immunoassay. Serum levels were compared with levels from 34 age-matched and gender-matched volunteer blood donors.


RESULTS
Endostatin levels were significantly higher in sera from sarcoma patients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002; Mann-Whitney U test). Significant elevations also were noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels > 2 standard deviations above the control mean (55 ng/mL) were associated with an increased risk of tumor recurrence after resection (P = 0.047; log-rank test).


CONCLUSIONS
Serum endostatin, VEGF, and bFGF levels are elevated in patients with soft tissue sarcoma. Elevated endostatin levels appear to be associated with tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as potential targets for therapy warrants further study.
Feldman
A L
AL
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pak
H
H
Yang
J C
JC
Alexander
H R
HR
Libutti
S K
SK
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D003094:Collagen / Q000097:blood*; D043170:Collagen Type XVIII; D018450:Disease Progression; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D008222:Lymphokines / Q000097:blood; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009389:Neovascularization, Pathologic; D010446:Peptide Fragments / Q000097:blood*; D012189:Retrospective Studies; D012307:Risk Factors; D012509:Sarcoma / Q000097:blood*; D012983:Soft Tissue Neoplasms / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D014408:Biomarkers, Tumor; D043170:Collagen Type XVIII; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D003094:Collagen