Angiopoietins 1 and 2 and Tie‐2 receptor expression in human ductal breast disease

Abstract

This study aimed to identify the involvement of the angiopoietin/Tie-2 receptor system in breast cancer development, progression, metastasis and angiogenesis. We quantified and correlated angiopoietin-1 (Ang-1), Ang-2 and Tie-2 expression in sections of normal human breast, benign and premalignant hyperplastic tissue, pre-invasive and invasive cancer, and compared these findings with our previously published data on vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the same samples. A breast cancer tissue microarray was used to evaluate the prognostic value of these factors. Histological analysis revealed a significant decrease in Ang-1 expression (P = 0.001) and an inverse correlation with MVD (r = -0.442, P = 0.008) and VEGF (r = -0.510, P = 0.002) in the non-invasive lesions. In contrast Ang-2 expression increased significantly (P = 0.0004) with increasing severity of lesion and correlated with MVD (r = 0.570; P = 0.0002), while Tie-2 expression remained relatively unchanged. Expression of all three factors was reduced in invasive breast cancer and did not correlate with oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), lymph node status or tumour grade. These data suggest that a change in the angiopoietin balance in favour of Ang-2 is associated with the angiogenic switch at the onset of hyperplasia in the breast. However, angiopoietins and the Tie-2 receptor are not related to known prognostic indicators in invasive breast cancer.