Urinary angiostatin levels are elevated in patients with epithelial ovarian cancer

Objective. The poor prognosis associated with epithelial ovarian cancer (EOC) is due to the lack of overt early symptoms and the absence of reliable diagnostic screening methods. Since many tumors over express angiogenic regulators, the purpose of this study was to determine whether elevated levels of the angiogenic or angiostatic molecules vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), endostatin (ES), and angiostatin (AS) were elevated in plasma and urine from patients with EOC. Methods. VEGF, HGF, ES and AS were assayed by ELISA in samples from pilot cohort consisting of healthy women (N = 48: pre-menopausal N = 23, post-menopausal N = 25), women with benign gynecological disease (N = 54), patients with primary peritoneal cancer (PP) (N = 2) and EOC (N = 35). Wherever possible, parallel serum samples were measured for CA125 levels by ELISA. Results. AS was the angioregulator that independently discriminated EOC patients from healthy individuals. Levels of urinary AS (uAS) from healthy individuals or women with benign gynecological disease averaged 21.4 ng/mL +/- 3.7 and 41.5 ng/mL +/- 8.8, respectively. In contrast, uAS averaged 115 ng/mL +/- 39.2 and 276 ng/mL +/- 45.8 from women with Stage I (N = 6) and late stage (N = 31) EOC, respectively. Furthermore, uAS was elevated in EOC patients regardless of tumor grade, stage, size, histological subtype, creatinine levels, menopausal status, or patient age, but appeared to complement CA125 measurements. Conclusions. Levels of AS are elevated in the urine of patients with EOC and may be of diagnostic and/or prognostic clinical importance. Further studies of uAS as a biomarker for EOC alone or in combination with other markers are warranted. (C) 2009 Elsevier Inc. All rights reserved.