title: Expression of thioredoxin system and related peroxiredoxin proteins is associated with clinical outcome in radiotherapy treated early stage breast cancer.
abstract: OBJECTIVE
  Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Expression of the thioredoxin system proteins (thioredoxin, thioredoxin reductase and thioredoxin interacting protein) and downstream peroxiredoxins (I-VI), was examined in tumor specimens from early stage breast cancer patients, subsequently treated by breast conserving surgery and locoregional radiotherapy, to determine if redox protein expression is associated with clinical outcome.
  
  
  METHODS
  Nuclear and cytoplasmic expression was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors.
  
  
  RESULTS
  High expression of cytoplasmic peroxiredoxin-I correlated with a greater risk of local recurrence (p=0.009). When nuclear and cytoplasmic expression patterns were combined, patients with low nuclear but high cytoplasmic expression of peroxiredoxin-I increased significance (p=0.005). Both were independent factors (p=0.006 and 0.003) from multivariate analysis. Associations were obtained between tumor grade and nuclear thioredoxin interacting protein (p=0.01) and with cytoplasmic expression of peroxiredoxin-V (p=0.007) but not with peroxiredoxin-I suggesting that the latter may exert influence via regulation of oxidative stress rather than via altering the tumor phenotype.
  
  
  CONCLUSIONS
  Results highlight the potential of using redox protein expression, namely peroxiredoxin-I, to predict clinical outcome and support further studies to validate its usefulness as an independent prognostic, and potentially predictive, marker.
authors.affiliation: Division of Clinical Oncology, University of Nottingham, UK.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Woolston
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
authors.forename: David A L
authors.initials: DA
authors.lastname: Morgan
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D017382:Reactive Oxygen Species; D013879:Thioredoxins; D054464:Peroxiredoxins