Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas

BMC Cancer. 2011 Jun 21;11:262. doi: 10.1186/1471-2407-11-262.

Abstract

Background: Triple-negative breast cancer (TNBC) and basal-like breast cancer (BLBC) are breast cancer subtypes with an especially poor prognosis. 8-Hydroxydeoxyguanosine (8-OHdG) is a widely used marker of oxidative stress and the redox-state-regulating enzymes peroxiredoxins (PRDXs) are efficient at depressing excessive reactive oxygen species. NF-E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) are redox-sensitive transcription factors that regulate PRDX expression. This is the first study to assess oxidative stress and or cell redox state-regulating enzymes in TNBC and BLBC.

Methods: We assessed immunohistochemical expression of 8-OHdG, Nrf2, Keap1, PRDX III and PRDX IV in 79 women with invasive ductal breast carcinomas. Of these tumors, 37 represented TNBC (grade II-III tumors with total lack of ER, PR and human epidermal growth factor receptor 2 [HER2] expression). Control cases (n = 42) were ER-positive, PR-positive and HER2-negative. Of the 37 TNBCs, 31 had BLBC phenotype (TNBC with expression of cytokeratin 5/6 or epidermal growth factor receptor 1).

Results: Patients with TNBC had worse breast cancer-specific survival (BCSS) than the control group (p = 0.015). Expression of 8-OHdG was significantly lower in TNBC than in the non-TNBC group (p < 0.005). 8-OHdG immunostaining was associated with better BCSS (p = 0.01), small tumor size (p < 0.0001) and low grade (p < 0.0005). Keap1 overexpression was observed in the TNBC cohort (p = 0.001) and Keap1-positive patients had worse BCSS than Keap1-negative women (p = 0.014). PRDX IV was overexpressed in the TNBC vs. the non-TNBC group (p = 0.022).

Conclusions: Cellular redox state markers may be promising targets when elucidating the pathogenesis of TNBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cohort Studies
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kaplan-Meier Estimate
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction
  • Oxidative Stress*
  • Peroxiredoxin III / metabolism
  • Peroxiredoxins / metabolism
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Receptors, Estrogen
  • Receptors, Progesterone
  • 8-Hydroxy-2'-Deoxyguanosine
  • PRDX3 protein, human
  • PRDX4 protein, human
  • Peroxiredoxin III
  • Peroxiredoxins
  • Receptor, ErbB-2
  • Deoxyguanosine