In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections.We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF.We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo.Vascular endothelial growth factor (VEGF) is a potent mediator of tumor angiogenesis, including neovascularization in human breast cancer [1]. In breast cancer patients, high tumor VEGF levels, as assessed by immunohistochemistry or quantitative immunoassay, appear to correlate with poor prognosis and decreased overall survival for both node-positive and node-negative breast cancer patients [2-4]. VEGF exists in several isoforms; the shorter isoforms are diffusible proteins whereas the longer isoforms are sequestered in the extracellular matrix [5]. Proteolytic cleavage may convert the longer VEGF isoforms into soluble, bioactive forms in the extracellular space where they become available to endothelial cells [5]. Sex steroids have been shown to increase VEGF expression in normal breast tissue as well as in experimental breast cancer, both in vitro and in vivo [6-10], and an estrogen responsive element (ERE) has been identified in the promoter region of the gene for VEGF [11].Estrogen exposure is considered a major risk factor for development of breast cancer and the majority of breast cancers maintain their