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

Abstract

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. Cancer 2003;97:2767–75. © 2003 American Cancer Society. DOI 10.1002/cncr.11399