BACKGROUND, Solid tumors are angiogenesis dependent, and elevated levels of
proangiogenic cytokines have been reported in a variety of histologies. En
dostatin is an antiangiogenic fragment of the basement membrane protein, co
llagen XVIII. Because antiangiogenic protein fragments may be generated by
tumor-derived proteases, the authors sought to determine whether circulatin
g levels of endostatin were elevated in patients with localized soft tissue
sarcoma.
METHODS, The authors analyzed preoperative serum levels of endostatin, vasc
ular endothelial growth factor (VEGF), and basic fibroblast growth factor (
bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with sof
t tissue sarcoma. For each serum sample, two aliquots were assayed in dupli
cate using a competitive enzyme immunoassay. Serum levels were compared wit
h levels from 34 age-matched and gender-matched volunteer blood donors.
RESULTS. Endostatin levels were significantly higher in sera from sarcoma p
atients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, resp
ectively; P = 0.0002; Mann-Whitney U test). Significant elevations also wer
e noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively).
Furthermore, endostatin levels > 2 standard deviations above the control me
an (55 ng/mL) were associated with an increased risk of tumor recurrence af
ter resection (P = 0.047; log-rank test).
CONCLUSIONS, Serum endostatin, VEGF, and bFGF levels are elevated in patien
ts with soft tissue sarcoma. Elevated endostatin levels appear to be associ
ated with tumor aggressiveness. The role of these cytokines in sarcoma angi
ogenesis and as potential targets for therapy warrants further study. Cance
r 2001;91:1525-9. (C) 2001 American Cancer Society.