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

François Pepin, Nicholas Bertos, Julie Laferrière, Svetlana Sadekova, Margarita Souleimanova, Hong Zhao, Greg Finak, Sarkis Meterissian, Michael T Hallett, Morag Park

INTRODUCTION: Angiogenesis represents a potential therapeutic target in breast cancer. However, responses to targeted anti-angiogenic therapies have been reported to vary among patients. This suggests that the tumor vasculature may be heterogeneous and that an appropriate choice of treatment would require an understanding of these differences. METHODS: In order to investigate whether and how the breast tumor vasculature varies between individuals, we have isolated tumor-associated and matched normal vasculature from 17 breast carcinomas by laser capture microdissection, and generated gene expression profiles. Since 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. RESULTS: We identify differences between tumor and normal vasculature, and 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 PDGFR) are differentially expressed between subtypes. Taking these subtypes into account has allowed us to derive a vascular signature associated with disease outcome. CONCLUSIONS: 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 towards the improved design and targeting of anti-angiogenic therapies.