Elevated serum endostatin is associated with poor outcome in patients with non-Hodgkin lymphoma

BACKGROUND. Endostatin is a cleaved fragment of collagen Type XVIII and has antiangiogenic activity. The clinical significance of circulating, soluble endostatin (S-endostatin) is not known. METHODS. Pretreatment S-endostatin and serum vascular endothelial growth factor (S-VEGF) levels were measured in 143 patients with non-Hodgkin lymphoma (NHL) using competitive enzyme immunoassays and were compared with the levels from a control group (n = 24 participants). RESULTS. S-endostatin levels varied widely from 4.5 ng/mL to 116 ng/mL (median, 29.6 ng/mL), and the median level was higher in patients with NHL compared with patients in the control group (16.4 ng/mL; P = 0.05). High S-endostatin levels were associated with advanced disease stage (P < 0.0001) and high serum VEGF levels at diagnosis (P = 0.017). The median 5-year survival rate for patients who had S-endostatin concentrations within the highest tertile (> 36.0 ng/mL) was only 34% compared with 57% in patients who had lower S-endostatin levels (P = 0.019). A high S-endostatin level also was associated with a poor outcome in patients with large cell diffuse and immunoblastic lymphoma, which was the largest subgroup within the series (n = 60 patients). Patients who had high pretreatment levels of both S-VEGF and S-endostatin had particularly poor outcomes. High S-endostatin levels had an independent, adverse influence on survival it was entered as a factor into a multivariate analysis together with the factors included in the International Prognostic Index (relative risk, 1.80; 95% confidence interval, 1.08-2.98; P = 0.0024). CONCLUSIONS. High pretreatment levels of S-endostatin are associated with high serum VEGF levels and poor survival in patients with NHL. Prospective studies are warranted to establish the clinical value of longitudinal S-endostatin measurements. (C) 2003 American Cancer Society.