Abstract 1382: Increased expression of placental growth factor is linked with shortened survival of patients with advanced ovarian cancer

Abstract

Abstract Background: Ovarian cancer (OC) is the leading cause of gynecologic cancer death in the United States. Survival in advanced OC is highly variable; some patients are cured of their disease with a combination of surgery and systemic chemotherapy, while the majority of patients develop recurrence and ultimately die of metastatic OC. While markers of poor prognosis within advanced OC exist, they have not translated to changes in therapy or outcomes. Vascular growth factors are important soluble mediators of tumor growth, vasculogenesis and angiogenesis that may be targeted therapeutically. We therefore explored the association between plasma levels of vascular growth factors and clinical outcomes in advanced OC. Methods: We enrolled 200 patients with OC or benign surgical conditions from the Mayo Ovarian SPORE Biospecimens Core. Presurgical plasma samples from patients with advanced OC (AJCC Stage III and IV, n = 100), early stage OC (Stage I and II, n = 50), and benign surgical conditions (n = 50) were assayed for vascular growth factors via multiplex electrochemiluminescence and by ELISA. Differences in plasma levels between benign, early, and advanced OC patient groups were assessed using plate-adjusted linear models. Associations between plasma levels of vascular growth factors and overall survival in advanced OC patients were assessed by Cox proportional hazards models. Results: Both vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels were increased in patients with advanced OC (mean ng/mL = 130.8, p = 0.004; mean ng/mL = 20.1, p = 0.025, respectively) compared to patients with early stage (mean ng/mL = 75.1 and 19.0 respectively) and benign conditions (mean ng/mL = 86.8 and 15.0, respectively). An increase in PlGF levels was associated with poor overall survival in patients with advanced OC (HR = 2.52, p = 0.005), while increase in VEGF levels were of borderline significance (HR = 1.21, p = 0.061) Conclusions: Soluble PlGF and VEGF are increased in the setting of advanced OC. Increased plasma PlGF is strongly linked to poor prognosis, while VEGF levels have a borderline association with prognosis. These data provide a rationale for therapeutic targeting of both VEGF and PlGF. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1382. doi:1538-7445.AM2012-1382