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

• Published in: PloS one Vol. 11; no. 1
• Main Authors: Nalwoga, Hawa, Ahmed, Lavina, Arnes, Jarle B, Wabinga, Henry, Akslen, Lars A
• Format: Journal Article
• Language: English
• Published: Public Library of Science 13.01.2016
• Subjects: Breast tumors; Development and progression; Health aspects; Phosphotransferases; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146823

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<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[alpha] expression had significantly higher MVD (p = 0.019) and higher pMVD (p = 0.027) than tumors with weak expression. High HIF-1[alpha] expression is significantly associated with Axl and VEGF expression, and with markers of poor prognosis in this series of breast cancer, suggesting HIF-1[alpha] and Axl as potential therapeutic targets in African breast cancer.