title: Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas.
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.
authors.affiliation: Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland. peeter.karihtala@oulu.fi
authors.forename: Peeter
authors.initials: P
authors.lastname: Karihtala
authors.forename: Saila
authors.initials: S
authors.lastname: Kauppila
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.lastname: Arja-Jukkola-Vuorinen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D061105:Peroxiredoxin III / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D047908:Intracellular Signaling Peptides and Proteins; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C431364:KEAP1 protein, human; C495635:NFE2L2 protein, human; C516115:PRDX3 protein, human; C515980:PRDX4 protein, human