A prospective analysis of plasma endostatin levels in colorectal cancer patients with liver metastases.
BACKGROUND
Circulating inhibitors of angiogenesis have been suggested to affect the growth of distant micrometastatic disease in patients with cancer. This study was designed to evaluate circulating endostatin levels in colorectal cancer patients with liver metastases.


METHODS
Plasma samples from 30 colorectal cancer patients with liver metastases were analyzed for endostatin and vascular endothelial growth factor (VEGF) by using competitive enzyme immunoassays. Samples were compared with plasma from age- and sex-matched healthy controls; values >2 SD above the control mean were considered elevated.


RESULTS
Plasma endostatin levels were significantly higher in the 30 cancer patients than controls (P < .0001) and correlated with preoperative VEGF levels (P = .0008). Eighteen patients underwent surgical treatment (liver resection, n = 10; or isolated hepatic perfusion with melphalan, n = 8). Seventeen treated patients were available for follow-up. Eight of 11 patients who progressed had elevated plasma endostatin levels at the time of progression. None of six patients who remained progression free had elevated endostatin levels at last follow-up (P = .02).


CONCLUSIONS
Plasma endostatin levels are elevated in colorectal cancer patients with liver metastases and correlate with VEGF levels. Elevated endostatin levels during follow-up are associated with disease progression. Understanding the role of endogenous endostatin in cancer patients may lead to novel strategies to inhibit tumor angiogenesis.
Feldman
A L
AL
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Alexander
H R
HR
Bartlett
D L
DL
Kranda
K C
KC
Miller
M S
MS
Costouros
N G
NG
Choyke
P L
PL
Libutti
S K
SK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000097:blood* / Q000378:metabolism; D003094:Collagen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000097:blood*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000556:secondary*; D008222:Lymphokines / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen