Serum Vegf-A May Predict Prognosis In Patients With Uterine Cervical Cancer

Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including uterine cervical cancer (CC). 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 CC. Methods: A total of 115 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IIB CC who were treated at Tottori University Hospital between 2006 and 2015 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. Survival analysis was performed with 86 patients treated between 2006 and 2013. 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 CC patients. 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 313, 8404 and 67.2 pg/ml, respectively. The levels of VEGF-A in patients with lymph node involvement were significantly higher than those in patients without it. On the contrary, the levels of VEGFR1 in patients with lymph node involvement were significantly lower than those in patients without it. Both histological types and FIGO stage were not related to levels of these angiogenic factors. We found a significant positive correlation between VEGF-A levels and the maximum tumor diameter. There was a significant negative correlation between VEGFR1 levels and the maximum tumor diameter. The overall survival rate was significantly lower in FIGO stage IIB than stage IB- IIA patients. 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 (92.9% vs. 72.8%, P = 0.014). 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. Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for CC. Citation Format: Mayumi Sawada, Tetsuro Oishi, Hiroaki Komatsu, Hiroaki Itamochi, Michiko Nonaka, Seitya Sato, Jun Chikumi, Sinya Sato, Sinya Sato, Muneaki Shimada, Tasuku Harada. Serum VEGF-A may predict prognosis in patients with uterine cervical 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 3386.