Angiogenesis and inflammation in ductal carcinoma in situ of the breast.

Abstract

Several recent studies suggest that vascular density may be an independent prognostic indicator in invasive carcinoma of the breast. Increased vascularity has also been shown in ductal carcinoma in situ (DCIS). The prognostic significance of the inflammatory infiltrate in mammary carcinoma is more controversial, but it could affect angiogenesis by releasing angiogenic factors and digesting matrix. Vascularity and inflammation have been studied in 41 examples of pure DCIS, classified using the method of Holland et al. Immunohistochemistry was performed with antibodies to von Willebrand factor, CD3, CD8, CD45RO, CD45RA, CD20, CD68, and c-erB-2. The main pattern of inflammation was clusters of B and T cells situated either adjacent to involved ducts or in the interductal stroma. Typically, these clusters were around vessels with plump endothelium suggestive of high endothelial venules. A less prominent pattern was a diffuse stromal infiltrate of macrophages and T cells. There were two patterns of increased vascularity associated with DCIS: necklaces of vessels close to the involved ducts and vessels arranged diffusely in the interductal stroma. Each pattern of inflammation and of vascularity was graded semi-quantitatively. Increased stromal vascularity was associated with the perivascular clusters of inflammation; both were associated with c-erB-2 expression and extent of the DCIS. Necklaces of vessels were associated with the diffuse inflammation. Perivascular inflammation and c-erB-2 (but neither pattern of vascularity) were associated with poor differentiation of the DCIS. Thus, different patterns of inflammation are associated with different patterns of vessels. The clusters of B and T cells may be recruited via high endothelial venules induced by the DCIS. Cytokines released by the DCIS and/or the inflammatory cells (clusters or diffuse) may stimulate the two patterns of new vessel formation.