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

Inhibition of hypoxia-inducible factor (HIF) and Axl receptor tyrosine kinase is being evaluated for targeted therapy in solid tumors. Both HIF-1[alpha] 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[alpha] 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[alpha] 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[alpha] 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[alpha] expression was associated with increased Axl (p = 0.007), VEGF (p