The Specific Shapes of Capillaries are Associated with Worse Prognosis in Patients with Invasive Breast Cancer

Abstract Purpose Angiogenesis is considered essential for tumor progression; however, whether histological counting of blood vessel numbers, expressed as microvessel density (MVD), can be a prognostic factor in breast cancer remains controversial. It has been suggested that the specific morphology of blood vessels such as glomeruloid microvascular proliferation (GMP) was associated with clinical parameters. Here, we aimed to clarify the significance of MVD with revised immunohistochemistry and to identify new blood vessel shapes that predict prognosis in breast cancer. Methods Four hundred and eleven primary breast cancer specimens were collected, and the sections were immunohistochemically stained with CD31 (single staining) and CD31 and Collagen IV (double staining). The prognosis of patients was examined according to MVD value, and the presence of GMP and other blood vessels with other specific shapes. Results With a sensitive and specific double immunostaining, high MVD value was associated even with better survival. The presence or absence of GMP was not related to patients’ prognosis. By contrast, patients with deep-curved capillaries surrounding tumor cell nests (C-shaped) or excessively branched capillaries near tumor cell nests showed a significantly poor prognosis. The presence of these capillaries was also correlated with clinicopathological parameters such as Ki-67 index and histological grade. Conclusion Even though MVD is widely used as a marker of angiogenesis, the complex morphology of blood vessels is significantly associated with clinical parameters. To estimate patients’ prognosis, the shape of blood vessels should also be taken into account.