VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) EXPRESSION AND ANGIOGENESIS IN PATIENTS WITH DUCTAL CARCINOMA IN-SITU OF THE BREAST

BACKGROUND. Prior studies have indicated that ductal carcinoma in situ (DCIS) lesions are capable of inducing a vascular stroma. However, th e mechanisms responsible for angiogenesis in DCIS currently are not de fined. The goal of this study was to determine the relationship betwee n the expression of the angiogenic cytokine vascular permeability fact or (VPF), also known as vascular endothelial growth factor (VEGF), and angiogenesis in patients with DCIS. METHODS. Forty-six breast biopsie s with DCIS were characterized with regard to histologic features on h ematoxylin and eosin stained sections, and microvessel density and dis tribution using sections immunostained for factor VIII-related antigen . In addition, in situ hybridization was performed on formalin fixed, paraffin embedded sections using S-35 labeled riboprobes specific for VPF/VEGF. RESULTS. VPF/VEGF expression by tumor cells in DCIS was grea ter 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 angio genesis in these lesions. Among 22 cases with strong VPF/VEGF mRNA exp ression, the median microvessel count was 100 +/- 30.6 vessels/field. In contrast, among 24 cases with low level VPF/VEGF mRNA expression, t he median microvessel count was 71 +/- 48.6 vessels/field (P = 0.04). In addition, high grade DCIS lesions more commonly were associated wit h strong VPF/VEGF mRNA expression than low grade lesions, but the resu lts were not statistically significant. CONCLUSIONS. These findings su ggest that VPF/VEGF is an important angiogenic factor in patients with DCIS. (C) 1997 American Cancer Society.