Strong Expression of Hypoxia-Inducible Factor-1? (HIF-1?) Is Associated with Axl Expression and Features of Aggressive Tumors in African Breast Cancer.

ABSTRACT: Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1? and Axl influence tumor growth and metastatic potential, and they have been linked to treatment failure in many cancers. However, there is a lack of reports on HIF-1? expression in African breast cancer, which has a poor prognosis, and novel treatment targets must therefore be established. Here, we aimed to evaluate HIF-1? in relation to Axl expression, angiogenesis markers, and other tumor characteristics in a series of African breast cancer.Using immunohistochemistry, we examined 261 invasive breast cancers on tissue microarrays for HIF-1? and Axl as well as several other markers, and a subset of 185 cases had information on VEGF (vascular endothelial growth factor) expression, microvessel density (MVD), proliferating microvessel density (pMVD) and vascular proliferation index (VPI) for important comparisons.Strong HIF-1? expression was associated with increased Axl (p = 0.007), VEGF (p<0.0005), and p53 (p = 0.032) expression, as well as high tumor cell proliferation by Ki-67 (p = 0.006), and high tumor grade (p = 0.003). Tumors with strong HIF-1? expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression.High HIF-1? expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1? and Axl as potential therapeutic targets in African breast cancer.

SUBMITTER: Nalwoga H 

PROVIDER: S-EPMC4711940 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature