Abstract 3387: Serum VEGF-A may predict prognosis in patients with epithelial ovarian cancer
Authors: Komatsu Hiroaki , Oishi Tetsuro , Itamochi Hiroaki , Sawada Mayumi , Nonaka Michiko , Sato Seiya , Chikumi Jun , Sato Shinya , Shimada Muneaki , Harada Tasuku 
Published: July 2016

Abstract
Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including epithelial ovarian cancer (EOC). The vascular endothelial growth factor (VEGF) family is one of the major pathways involved in tumor angiogenesis. The aim of this study was to determine whether serum levels of these angiogenic factors could be used as biomarkers in patients with EOC.
Methods: A total of 133 patients with EOC who were treated at Tottori University Hospital between 2006 and 2014 were enrolled in this study. The study was approved by the Institutional Review Board of the School of Medicine of Tottori University. All patients gave written informed consent before the collection of specimens according to institutional guidelines. Serum samples were collected before initial surgery and levels of VEGF-A, -C and VEGFR1 were analyzed by enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the levels of VEGF-A, -C, and VEGFR1 and clinicopathologic variables. We also determined the mRNA expression VEGF-A, -C, and VEGFR1 by real-time RT-PCR in fresh frozen tumors and the protein expression by immunohistochemical staining in paraffin-embedded tumors from EOC patients. Additionally, serum samples were collected before and after bevacizumab treatment, and levels of angiogenic factors were examined.
Results: The mRNA and protein expressions of VEGF-A, -C, and VEGFR1 were strongly observed in the cancer cells. Median levels of serum VEGF-A, -C and VEGFR1 were 284, 4861 and 417 pg/ml, respectively. The levels of VEGF-A ans VEGFR1 in patients at stage III-IV were significantly higher than those in patients at stage I-II. Both histologic subtypes and lymph node involvement were not related to levels of these angiogenic factors. We found a significant positive correlation between VEGF-A levels and the ascitic volume. The overall survival rate was significantly lower in FIGO stage III or IV patients with EOC. We set the cutoff value of these factors at the median levels of each angiogenic factors. The 5-year survival rate for patients with high VEGF-A levels was significantly lower than those with low levels (60.7% vs. 45.5%, P = 0.029). Both VEGFR1 and VEGF-C levels were not related to outcome of patients. Multivariate analysis revealed that serum VEGF-A level and FIGO stage were independent prognostic factors. VEGF-A levels dramatically decreased after treatment with bevacizumab.
Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for EOC. Further study is needed to determine if could be predictive biomarker.
Citation Format: Hiroaki Komatsu, Tetsuro Oishi, Hiroaki Itamochi, Mayumi Sawada, Michiko Nonaka, Seiya Sato, Jun Chikumi, Shinya Sato, Muneaki Shimada, Tasuku Harada. Serum VEGF-A may predict prognosis in patients with epithelial ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3387.