Circulating levels of VEGF-A, VEGF-D and soluble VEGF-A receptor (sFIt-1) in human breast cancer.

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 FIt-1 (sFIt-1). Circulating levels of VEGF-A, VEGF-D and sFIt-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 sFIt-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 sFIt-1 levels in both patient and control groups (p < 0.0001). In addition, the ratio of sFIt-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 sFIt-1 and VEGF-A in the circulation. Measuring the sFIt-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.