VEGF Expression is Associated with Negative Estrogen Receptor Status in Patients with Breast Cancer

Abstract

The aim of this study was to analyze the association between vascular endothelial growth factor (VEGF) expression on tumor cells and other clinicopathologic parameters in breast cancer that could give additional information on its prognostic significance. Immunohistochemical analysis of expression of VEGF, estrogen (ER) and progesterone receptor (PR), HER-2/neu, and Ki67 was performed in 233 breast cancers. VEGF expression estimated semiquantitatively was correlated with all the above-mentioned parameters as well as with clinicopathologic characteristics of breast cancer such as menopausal status of patients, tumor size, histologic and nuclear grade, vascular invasion, and lymph node status. Most of the tumor cells and some stromal components expressed VEGF. A higher percentage of VEGF-positive tumor cells was present in premenopausal patients and in ER-negative tumors. In postmenopausal patients tumors with a higher expression of VEGF were associated not only with ER-negative but also with HER-2/neu-positive tumor cells. These ER-negative tumors were characterized by a higher proliferative activity. Angiogenic switch as well as proliferative activity of breast cancer cells probably are unfavorably dependent on estrogen activity. This negative correlation between VEGF expression and ER status may not only shed more light on tumor biology but may also have future therapeutic implications.

Vascular endothelial growth factor and its relationship to the prognosis and treatment of breast, ovarian, and cervical cancer

“…Another study showed that estrogen regulates VEGF expression but that estrogen receptor is also critical in determining the transcription of VEGF mRNA [46]. Some data suggest that ER and VEGF are inversely correlated; other data imply that estrogen induces VEGF expression and activity [47]. In a clinical case-control study comparing serum VEGF levels of 200 breast cancer patients with 88 healthy controls, it was shown that elevated levels of serum VEGF were observed in patients with invasive ductal cancer, ductal carcinoma in situ, and estrogen-receptor-positive tumors, but not with lobular carcinoma in situ or estrogenreceptor-negative tumors [48].…”

Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis

“…Expression of VEGF-A has been found to be upregulated and suggested to be associated with progression of certain types of human tumours such as lung (Han et al, 2001), eosophageal (Kleespies et al, 2005) and colorectal cancers (Des Guetz et al, 2006). Studies on human breast cancer reported a significant relationship between high expression of VEGF-A and tumours with higher proliferation rate, negative oestrogen receptor status (Fuckar et al, 2006) and poor prognosis (Linderholm et al, 1999).…”

89Zr-Bevacizumab PET Imaging in Primary Breast Cancer

“…A molecular target of interest in this respect is vascular endothelial growth factor (VEGF)-A. VEGF-A is involved in the development and maintenance of tumor angiogenesis and is involved early during tumorigenesis. Various studies have reported overexpression of VEGF-A in the breast cancer microenvironment, compared with normal breast tissue (2)(3)(4)(5). All VEGF-A splice variants are bound by the clinically used monoclonal antibody bevacizumab.…”