Co-expression of angiogenic markers and associations with prognosis in advanced epithelial ovarian cancer: A Gynecologic Oncology Group study

Objectives: The aim of this study was to explore the co-expression and prognostic relevance of thrombospondin-1 (THBS-1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and VEGF receptor 1 (VEGFR-1) in epithelial ovarian cancer (EOC). Methods: Frozen tumor specimens with defined p53 status were obtained from 67 patients with previously untreated advanced-stage EOC who participated in a Gynecologic Oncology Group specimen-banking protocol and a phase III treatment protocol. Relative expression of the angiogenic markers was quantified by immunoblot analysis and categorized at the median angiogenic marker/actin ratio. p-values are provided as an indication of confidence in the results and to prioritize further testing. Results: An association was observed between categorized VEGF and p53 overexpression (p = 0.022), and between VEGFR-1 and race (p = 0.027) or histologic subtype (p = 0.007). Unadjusted Cox regression analyses indicated that high compared with low THBS-1, but not VEGF or VEGFR-1, was associated with an increased risk of disease progression (hazard ratio [HR] = 2.19; 95% confidence interval [CI] = 1.29-3.71; p = 0.004) and death (HR = 1.93; 95% CI = 1.12-3.32; p = 0.018) whereas bFGF was associated with a reduced risk of disease progression (HR = 0.60; 95% CI = 0.36-0.99; p = 0.046) and death (HR = 0.54; 95% CI = 0.32-0.93; p = 0.026). After adjusting for prognostic factors including clinical characteristics and p53 overexpression, THBS-1 but not bFGF, VEGF or VEGFR-1 was associated with progression-free and overall survival. Conclusions: These data suggest that high THBS-1 is an independent predictor of worse progression-free and overall survival in women with advanced-stage EOC. A larger prospective study is warranted for validation of these findings.