Her-2/neu overexpression is associated with thrombospondin-1-related angiogenesis and thrombospondin-1-unrelated lymphangiogenesis in breast cancer

Abstract

Introduction: Her-2/neu overexpression is linked to poor prognosis and is a significant predictor of the response to trastuzumab (i.e., herceptin) therapy in breast cancer patients. Her-2/neu promotes angiogenesis with thrombospondin-1 (TSP-1) as a mediator in breast cancer development and progression. However, the clinical quantitative evaluation of Her-2/neu and specified localization of TSP-1 are currently lacking. Materials and methods: In this study, immunohistochemistry was performed to elucidate the in vivo relationships between Her-2/neu and TSP-1 expression, angiogenesis, and lymphangiogenesis in breast cancer. Based on immunohistochemical staining for anti-Her-2/neu and related quantitative scoring of tumor cells, 28 individuals with high Her-2/Neu expression (i.e., with a score of ≥2.0) were recruited into the study group. Another 28 individuals with low Her-2/neu (i.e., with a score of 2.0, with 2.0 as the cut-off value) had a significantly lower microvessel density, compared to individuals with low-TSP-1 expression (p = 0.018). However, the lymphatic vessel density was not significantly different from the TSP-1 levels (p = 0.333). Conclusion: Our in vivo results showed that Her-2/neu affects the biological manifestations of breast cancer by increasing angiogenesis (which is TSP-1-related) and lymphangiogenesis, which is TSP-1-unrelated).

Keywords

• Angiogenesis
• Automated cellular imaging system
• Breast cancer
• Her-2/neu
• Lymphangiogenesis
• Thrombospondin-1
• Tumor-stroma interaction