Vasohibin-1 in human breast carcinoma: a potential negative feedback regulator of angiogenesis.

Vasohibin-1 is a recently identified negative feedback inhibitor or suppressor of angiogenesis induced by vascular endothelial growth factor (VEGF)-A. The status of vasohibin-1 in human breast carcinoma has not been examined. We examined 151 breast specimens including 98 cases of invasive ductal carcinoma (IDC), 12 of ductal carcinoma in situ (DCIS), 16 of fibroadenoma (FA), six of inflammatory lesion, nine of fibrocystic change and seven of non-pathological breast tissue. We immunolocalized vasohibin-1 and compared its immunoreactivity to that of VEGF-A, basic fibroblastic growth factor (bFGF), VEGF receptor 2 (Flk-1), CD31, CD34 and Ki-67/MIB-1. The correlation of vasohibin-1 immunoreactivity with overall survival (OS), and disease-free survival (DFS) of the patients with breast carcinoma was also evaluated. In addition, we evaluated Ki-67 and CD31, and Ki-67 and vasohibin-1 double-immunostaining for further characterization of neovascularization. Vasohibin-1 was detected in endothelial cells of human breast and its immunodensity was significantly higher in IDC and inflammatory lesions than the other types (P<0.001). In addition, a significant positive correlation was detected between vasohibin-1 and VEGF-A, bFGF or Flk-1 (P<0.001). There was also positive associations between vasohibin-1 and OS (P=0.004) and between vasohibin-1 and DFS (P<or=0.001) in carcinoma cases. Results of double-immunostaining demonstrated the ratio of Ki-67-positive cells among vasohibin-1-positive endothelial cells (46.5%) was significantly higher than those among CD31-positive cells (23.5%). This is the first study demonstrating the status of vasohibin-1 in human breast lesions, which indicates that vasohibin-1 is associated with neovascularization and may especially play important roles in the regulation of intratumoral angiogenesis in human breast cancer.