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A Prospective Analysis of Plasma Endostatin Levels in Colorectal Cancer Patients With Liver Metastases

From the Surgery Branch, National Cancer Institute (ALF, HRA, DLB, KCK, MSM, NGC, SKL) and the Diagnostic Radiology Department (PLC), Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland.

Correspondence: Address correspondence and reprint requests to: Steven K. Libutti, MD, Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2B07, 9000 Rockville Pike, Bethesda, MD 20892; Fax: 301-402-1788; E-mail: libuttis{at}mail.nih.gov

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.

Key Words: Angiogenesis • Endostatin • Colorectal cancer • Liver metastasis • Vascular endothelial growth factor

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