HER2 Is Unlikely to Be Involved in Directly Regulating Angiogenesis in Human Breast Cancer

Abstract

Angiogenesis is a fundamental component of oncogenesis. Angiogenic factors such as vascular endothelial growth factor (VEGF) and platelet derived-endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) are generated from tumor cells to provide tumor growth and are thought to be regulated via the HER2 oncogene, whose amplification is the most common genetic alteration in breast cancer. The present study aimed to evaluate the immunoreactivity of angiogenic factors (VEGF, PD-ECGF/TP) and microvessel density (MVD) via epidermal growth factor receptor (EGFR) and HER2, and to correlate their expression with clinicopathologic features. Two hundred one invasive human breast cancer specimens were tested immunohistochemically for the expression of these proteins. In addition, MVD was examined using computerized image analysis. VEGF could be an additional interesting prognostic variable, as it was significantly associated with tumor grade (P=0.002), stage (P=0.018), and negative estrogen receptor status (P=0.011). EGFR was significantly related to invasive ductal carcinoma (P=0.030), tumor grade (P=0.009), VEGF expression (P=0.013), PD-ECGF/TP expression (P=0.024), and MVD (P=0.050). The finding that VEGF is not correlated to MVD does not rule out a crucial role of VEGF as a key factor in angiogenesis. HER2 could not be correlated to MVD, VEGF expression, or PD-ECGF/TP expression, indicating that this factor is unlikely to be involved in directly regulating angiogenesis, whereas the significant correlations between EGFR and histologic tumor type, tumor grade, the angiogenic factors VEGF and PD-ECGF/TP, and MVD point out that EGF is the major modulating growth factor for angiogenesis in breast cancer.

Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy

“…Although HER2 signaling is believed to promote tumour angiogenesis (Kumar and Yarmand-Bagheri, 2001), we found no association between HER2 overexpression and MVD, in keeping with previous results (Vogl et al, 2006). In contrast, others observed an association of MVD and HER2 overexpression in small series of patients with node-negative disease (Koukourakis et al, 2003).…”

Comparison of microvessel density with prognostic factors in invasive ductal carcinomas of the breast

“…In the literature, some studies have reported that there is no relationship between mVD and prognostic parameters such as patient's age (25,27), histological grade (28), lymphovascular invasion (9), estrogen and progesterone receptor status (27), HEr2/neu overexpression (27). On the other hand, there are also some other studies that found a significant relationship between high mVD and patient's age (29), high histologic grade (16,25,27), presence of lymphovascular invasion (30), estrogen (16,22) and progesterone receptor negativity (22) and HEr2/neu overexpression (31).…”

“…One of the reason of this may be using different antibodies such as CD34, CD31, Factor VIII and CD105 to highlight the microvessels (24,32,33). In the literature, some studies reported that the anti-CD34 monoclonal antibody is more sensitive than the anti-CD31 antibody and anti-factor VIII-related antigens in the calculation of mVD in breast cancer (31,32). Therefore, we used the anti-CD34 monoclonal antibody to calculate the mVD.…”

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.…”