BACKGROUND: To quantify tumour angiogenesis, microvessel density (MVD) has been widely used. We here present a novel angiogenesis marker, microvessel proliferation (MVP), based on dual immunohistochemical staining of nestin and Ki-67. Immature endothelial cells express nestin, and when co-expressed with the proliferation marker Ki-67, the number of proliferating immature blood vessels can be measured. MATERIALS AND METHODS: Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index (VPI), the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels. RESULTS: High VPI was strongly associated with several markers of aggressive breast cancer, such as negative oestrogen receptor (ER) status (p = 0.003), high tumour cell proliferation by Ki-67 (p = 0.004), high p53 expression (p = 0.001), and five profiles for the basal-like phenotype (odds ratios (OR); range 3.4-6.3). Also, high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions (p < 0.0005), and adverse outcome in univariate and multivariate survival analysis (p = 0.034 and p = 0.022, respectively). CONCLUSION: Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features, basal-like phenotypes, interval presentation, and prognosis in this series of breast cancer.
BACKGROUND: To quantify tumour angiogenesis, microvessel density (MVD) has been widely used. We here present a novel angiogenesis marker, microvessel proliferation (MVP), based on dual immunohistochemical staining of nestin and Ki-67. Immature endothelial cells express nestin, and when co-expressed with the proliferation marker Ki-67, the number of proliferating immature blood vessels can be measured. MATERIALS AND METHODS: Microvessel proliferation was evaluated in 178 breast cancer samples and estimated by vascular proliferation index (VPI), the ratio between the number of vessels containing proliferating endothelial cells and the total number of immature vessels. RESULTS: High VPI was strongly associated with several markers of aggressive breast cancer, such as negative oestrogen receptor (ER) status (p = 0.003), high tumour cell proliferation by Ki-67 (p = 0.004), high p53 expression (p = 0.001), and five profiles for the basal-like phenotype (odds ratios (OR); range 3.4-6.3). Also, high VPI was significantly associated with interval detected breast cancer compared with screening detected lesions (p < 0.0005), and adverse outcome in univariate and multivariate survival analysis (p = 0.034 and p = 0.022, respectively). CONCLUSION: Microvessel proliferation is a novel marker of ongoing angiogenesis and was associated with aggressive tumour features, basal-like phenotypes, interval presentation, and prognosis in this series of breast cancer.
Authors: Ingunn M Stefansson; Maria Raeder; Elisabeth Wik; Monica Mannelqvist; Kanthida Kusonmano; Gøril Knutsvik; Ingfrid Haldorsen; Jone Trovik; Anne M Øyan; Karl-H Kalland; Anne Cathrine Staff; Helga B Salvesen; Lars A Akslen Journal: Oncotarget Date: 2015-04-30