Gene-expression profiling of microdissected breast cancer microvasculature identifies distinct tumor vascular subtypes

To investigate whether and how the breast tumor vasculature varies between individuals, we isolated tumor-associated and matched normal vasculature from 17 breast carcinomas by laser-capture microdissection, and generated gene-expression profiles. Because microvessel density has previously been associated with disease course, tumors with low (n = 9) or high (n = 8) microvessel density were selected for analysis to maximize heterogeneity for this feature.We identified differences between tumor and normal vasculature, and we describe two subtypes present within tumor vasculature. These subtypes exhibit distinct gene-expression signatures that reflect features including hallmarks of vessel maturity. Potential therapeutic targets (MET, ITGAV, and PDGFRβ) are differentially expressed between subtypes. Taking these subtypes into account has allowed us to derive a vascular signature associated with disease outcome.Our results further support a role for tumor microvasculature in determining disease progression. Overall, this study provides a deeper molecular understanding of the heterogeneity existing within the breast tumor vasculature and opens new avenues toward the improved design and targeting of antiangiogenic therapies.The growth of tumors beyond a certain size requires the recruitment of an adequate blood supply, which is supplied by abnormal angiogenesis. This involves the triggering of an "angiogenic switch" [1], whereby the tumor microenvironment enters a proangiogenic mode in response to hypoxia. This process is accompanied by increased levels of multiple proangiogenic factors, including vascular endothelial growth factor A (VEGFA) and platelet-derived growth factor B (PDGFB), as well as decreases in antiangiogenic factors such as endostatin. This leads to an increase in the number of proliferating endothelial cells, along with enhanced endothelial cell recruitment and migration toward the tumor bed [2].Because endothelial cells are considered to be genetically