Serum endostatin levels are elevated and correlate with serum vascular endothelial growth factor levels in patients with stage IV clear cell renal cancer

Clear cell renal carcinoma (CCRC) is a highly angiogenic tumor known to sec rete vascular endothelial cell growth factor (VEGF), Endostatin is an endog enous antiangiogenic agent with antitumor activity in mice. The purpose of this study was to evaluate serum levels of endostatin in normal subjects an d in patients with CCRC and to examine the relationship of these levels to circulating VEGF levels. Fifteen patients (mean age, 48 years) on a clinica l protocol for stage IV CCRC at the National Cancer Institute were included in the study. Archived prenephrectomy serum samples were analyzed for endo statin and VEGF concentrations. Endostatin and VEGF levels were compared wi th those of an age-matched group of volunteer blood donors (n = 18) using a competitive enzyme immunoassay, Data were analyzed using the Mann-Whitney U test and the Spearman rank correlation, Median serum endostatin levels we re 24.6 ng/ml (range, 15.1-54.0 ng/ml) in CCRC patients versus 14.1 ng/ml ( range, 1.0-19.3 ng/ml) in healthy controls (P < 0.0001). Median VEGF levels were 3.4 ng/ml (range, 0.1-11.2 ng/ml) and 2.5 ng/ml (range, 0.1-4.2 ng/ml ), respectively (P = 0.065). A highly significant correlation was observed between endostatin and VEGF levels among the CCRC patients (r = 0.81, P = 0 .0003) but not among controls (r = -0.22, P = 0.37). Endostatin levels are detectable in serum from healthy subjects as well as from CCRC patients, Le vels are significantly elevated and correlate with VEGF levels in CCRC pati ents. Elucidating the nature of this correlation may lend insight into the regulation of tumor angiogenesis in patients with renal cancer.