Serum VEGF levels and tissue activation of VEGFR2/KDR receptors in patients with breast and gynecologic cancer

Abstract

Objectives Vascular endothelial cell growth factor (VEGF) plays an important role in the biology of gynecological cancer, usually linked with aggressive tumour behaviour and a poor postoperative outcome. Yet, its role in benign breast/gynecological conditions is less clear. Methods Serum VEGF was analysed in a series of 49 patients with gynecological cancer and 61 patients with benign disease and compared to those of 12 normal female subjects. In addition, the activation status of VEGFR2/KDR receptors was investigated in formalin-fixed paraffin embedded tissues and related to VEGF. Results Mean serum levels of VEGF were significantly higher in patients with breast, endometrial and ovarian cancer compared to healthy controls and those with benign breast/gynecologic disease in the respective organs. A similar trend was noted in some cases of simple endometrial hyperplasia, fibroadenoma and fibrocystic disease of the breast. The expression of phosphorylated VEGFR2/KDR receptors was higher in breast, endometrial, ovarian cancer in patients with high VEGF serum levels and this reached a level of statistical significance when all malignancies were combined. Conclusions Serum VEGF levels are increased in patients with breast and gynecological malignancies, but this can not be considered pathognomonic for cancer as it is also increased in certain benign conditions, including cases of fibroadenoma, fibrocystic disease of breast and simple endometrial hyperplasia. Furthermore, high serum VEGF levels are closely related to the activation status of the VEGFR2/KDR receptor in cancer cells, indicating a stimulatory effect of serum VEGF on the VEGF pathway contributing to tumor progression.