Circulating Levels of Vegf-A, VEGF-D and soluble VEGF-A Receptor (sFlt-1) in Human Breast Cancer

Abstract

As circulating levels of vascular endothelial growth factor (VEGF-A) are raised in malignancy, the aim of this study was to investigate whether similar changes occur in two related factors, VEGF-D and the soluble VEGF-A receptor Flt-1 (sFlt-1). Circulating levels of VEGF-A, VEGF-D and sFlt-1 were determined by ELISA in 51 patients with primary breast cancer and matched healthy controls. Results were correlated with clinicopathological data. Whilst there was a difference in VEGF-A levels between patient and control groups (p=0.03), no such difference was observed for sFlt-1 or VEGF-D levels and there was no association between individual factors and the clinicopathological variables examined. However, there was a positive correlation between VEGF-A and sFlt-1 levels in both patient and control groups (p<0.0001). In addition, the ratio of sFlt-1 to VEGF-A was significantly different between patients and controls (p<0.0001) and was also associated with tumour size (p=0.01) within the patient group. During tumour progression there is a change in the relative amounts of sFlt-1 and VEGF-A in the circulation. Measuring the sFlt-1:VEGF-A ratio may have more significance than VEGF-A alone and further studies are needed to determine whether the ratio is of use as a prognostic marker or as a means of monitoring response to anti-angiogenic therapy in cancer.