HIF-2α as a prognostic marker for breast cancer progression and patient survival

Genet Mol Res. 2014 Jan 22;13(2):2817-26. doi: 10.4238/2014.January.22.6.

Abstract

Malignant cells show increased invasion potency in vitro and in vivo. This process is considered to be mediated by matrix-metalloproteases (MMPs). Hypoxia-inducible factor-2α (HIF-2α) may upregulate MMP-2 expression; however, little is known about the correlation between HIF-2α and MMP-2 expressions in breast cancer. The current study investigated this correlation immunohistochemically according to various clinical and pathological features in 102 paraffin-embedded archival tissue block specimens from patients with breast cancer. HIF-2α and MMP-2 expression was detected in 60.8% (62/102) and 65.7% (67/102) of tumor samples, respectively. HIF-2α expression was significantly correlated with tumor size (P = 0.019), lymph node involvement (P = 0.035), and metastasis (P = 0.035). MMP-2 expression was significantly associated with lymph node involvement (P = 0.043) and metastasis (P = 0.003). Univariate analyses revealed that HIF-2α (P = 0.001) and MMP-2 (P = 0.000) expressions were significantly associated with a poorer survival rate, as well as tumor size, lymph node invasion, and distant metastasis. Multivariate analysis revealed that HIF-2α (P = 0.003) and the T-stage (P = 0.000) were independent prognostic factors of overall survival. Spearman correlation analysis revealed that HIF-2α and MMP-2 expressions were significantly correlated (r = 0.990; P = 0.041). These results suggest that high HIF- 2α expression is associated with poor overall survival in patients with breast cancer, indicating that HIF-2α could be a valuable marker of breast cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymph Nodes / pathology
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Middle Aged
  • Prognosis
  • Survival Rate

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • endothelial PAS domain-containing protein 1
  • Matrix Metalloproteinase 2