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Keywords:

  • hypoxia-inducible factor;
  • HIF-1α;
  • prognosis;
  • breast carcinoma;
  • immunohistochemistry

Abstract

Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that is involved in tumour growth and metastasis by regulating genes involved in response to hypoxia. HIF-1α protein overexpression has been shown in a variety of human cancers, but only 2 studies have documented the prognostic relevance of HIF-1α expression in breast cancer. The aim of our study was to determine accurately the impact of HIF-1α expression on prognosis in a large series (n = 745) of unselected patients with invasive breast cancer in terms of overall survival, local recurrence and distant metastasis risk. HIF-1α expression was investigated using immunohistochemical assays on frozen sections, and correlated with patients' outcome (median follow-up = 13.5 years). Univariate (Kaplan-Meier) analysis showed that high levels of HIF-1α expression (cutoff = 10%) significantly correlated with poor overall survival (p = 0.019). HIF-1α expression correlated with high metastasis risk among the whole group of patients (p = 0.008). Multivariate analysis (Cox model) showed that the HIF-1α predictive value was independent of other current prognostic indicators. Moreover among node negative ones, HIF-1α expression was also significantly predictive of metastasis risk (p = 0.03) and of relapse (p = 0.035). All the data suggest that HIF-1α is associated with a worse prognosis in patients with invasive breast carcinoma. Furthermore HIF-1α immunodetection may be considered as a potential indicator for selecting patients who could benefit from specific therapies interfering with HIF-1α pathway. © 2005 Wiley-Liss, Inc.