Abstract
Angiogenesis is critical for the growth, invasion and metastasis of cancers. Extensive neovascularization and tumor thrombus also correlate with a poor prognosis in breast cancer (BC). Although anti-angiogenic agents have been the therapies of choice for BC, in particular for triple-negative BCs, predictive markers for anti-angiogenic agents are lacking. Microvascular density (MVD) is commonly used to assess the neovascularization in tumors. Compared with pan-endothelial markers such as CD31, CD34 and von Willebrand factor (vWF), CD105 has a higher specificity for MVD in tumor tissues. In this study, we aimed to determine the prognostic value of CD105 in BCs. Paraffin-embedded tissue blocks from 201 BC patients were formed into tissue microarrays. Evaluation of MVD revealed that a median of 11 microvessels determined by CD105 staining correlated significantly with the pathological characteristics of BCs and also with the survival of patients. The expression of CD105 correlated inversely with hormone receptor (HR) expression but positively with Her-2 expression. Univariate analysis indicated that CD105 is a superior predictor of disease-free survival (DFS) in stage I and II diseases; multivariate analysis indicated that only hormone receptors (HRs) are suitable for predicting overall survival (OS) in stage III disease. These findings reveal for the first time that MVD measured by CD105 staining correlates positively with Her-2 expression but negatively with HR expression. The significance of MVD on OS is more apparent in early stage BCs. CD105 has the potential to be used as a predictive marker for anti-angiogenic agents; the targeting of CD105 may also be a potential anticancer strategy.