Vascular permeability factor (vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast

Abstract

BACKGROUND. Prior studies have indicated that ductal carcinoma in situ (DCIS) lesions are capable of inducing a vascular stroma. However, the mechanisms responsible for angiogenesis in DCIS currently are not defined. The goal of this study was to determine the relationship between the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), and angiogenesis in patients with DCIS. METHODS. Forty-six breast biopsies with DCIS were characterized with regard to histologic features on hematoxylin and eosin stained sections, and microvessel density and distribution using sections immunostained for factor VIII-related antigen. In addition, in situ hybridization was performed on formalin fixed, paraffin embedded sections using 35S labeled riboprobes specific for VPF/VEGF. RESULTS. VPF/VEGF expression by tumor cells in DCIS was greater than that observed in adjacent benign ductal or lobular epithelial cells in 96% of the evaluable cases. Moreover, the degree of VPF/VEGF mRNA expression was significantly associated with the degree of angiogenesis in these lesions. Among 22 cases with strong VPF/VEGF mRNA expression, the median microvessel count was 100 ± 30.6 vessels/field. In contrast, among 24 cases with low level VPF/VEGF mRNA expression, the median microvessel count was 71 ± 48.6 vessels/field (P = 0.04). In addition, high grade DCIS lesions more commonly were associated with strong VPF/VEGF mRNA expression than low grade lesions but the results were not statistically significant. CONCLUSIONS. These findings suggest that VPF/VEGF is an important angiogenic factor in patients with DCIS.