Association between intratumoral free and total VEGF, soluble VEGFR-1, VEGFR-2 and prognosis in breast cancer

Vascular endothelial growth factor ( VEGF) receptors consist of three cell- membrane type receptors ( VEGFR- 1, VEGFR- 2 and VEGFR- 3), and soluble form of VEGFR- 1 ( sVEGFR- 1), an intrinsic negative counterpart of the VEGF. In this study, we measured intratumoral protein levels of free and total VEGF, VEGFR- 2 and sVEGFR- 1 from 202 primary breast cancer tissues and examined their prognostic values. A significant inverse correlation was found between free or total VEGF and oestrogen receptor ( ER) status ( P = 0.042 and 0.032, respectively). A univariate analysis showed that low sVEGFR- 1 and high total VEGF were significantly associated with poor prognosis in disease- free survival ( DFS) and overall survival ( OS). The ratio of sVEGFR- 1 to total VEGF was a strong prognostic indicator ( DFS: P = 0.008; OS: P = 0.0002). A multivariate analysis confirmed the independent prognostic values of total VEGF and the ratio of sVEGFR- 1 to total VEGF. In subgroup analysis, total VEGF was a significant prognostic indicator for ER- positive tumours but not for ER- negative tumours, whereas sVEGFR- 1 was significant for ER- negative tumours but not for ER- positive tumours. In conclusion, the intratumoral sVEGFR- 1 level, VEGF level and the ratio of sVEGFR- 1 to total VEGF are potent prognostic indicators of primary breast cancer, and might be relevant to ER status.