No amplifications of hypoxia-inducible factor-1α gene in invasive breast cancer: A tissue microarray study

Objective: Hypoxia Inducible Factor-1 (HIF-1) is an important transcription factor that stimulates tumour growth and metastases via several pathways, including angiogenesis and altered metabolism. Activation of HIF-1 depends on the levels of its α-subunit, which increase during hypoxia. Recent studies showed that the HIF-1α gene was amplified in prostate cancer, leading to overexpression of HIF-1α at normoxia. The aim of this study was to evaluate the presence of HIF-1α gene amplifications in invasive breast cancer as an explanation for HIF-1α protein overexpression. Methods: Protein and gene expression of HIF-1α were analyzed on a tissue microarray of 94 breast cancers by immunohistochemistry and fluorescent in situ hybridization (FISH), respectively. Results: Overexpression of HIF-1α protein was found in 58/94 (62%) of patients. No amplifications of the HIF-1α gene were detected. Conclusion: Increased protein levels of HIF-1α are not associated with amplification of the HIF-1α gene in human breast cancer. Therefore, other mechanisms than gene amplification must be responsible for HIF-α overexpression at normoxia.