title: Divergent behaviour of oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (HNE) in breast carcinogenesis.
abstract: OBJECTIVE
  To clarify the role of oxidative stress during breast carcinogenesis by studying the expression of 8-hydroxydeoxyguanosine (8-OHdG) (a marker of oxidative DNA damage) and 4-hydroxy-2-nonenal (HNE) (a marker of lipid peroxidation) during the different phases of breast carcinogenesis.
  
  
  RESULTS
  The study material consisted of a total of 219 patients: 31 with usual ductal hyperplasia (UDH), 25 with atypical ductal hyperplasia (ADH), 30 with ductal carcinoma in situ (DCIS) and 133 with invasive carcinoma. The expression of 8-OHdG and HNE were evaluated immunohistochemically. Both 8-OHdG (77.4%) and HNE (45.8%) expression was already seen in UDH lesions. Interestingly, the trend of these two immunostainings during breast carcinogenesis was diverse. 8-OHdG expression diminished significantly in invasive breast carcinomas compared to non-invasive lesions (P < 0.005 when set against non-invasive cohorts). Also within the same lesions, 8-OHdG expression was the most intensive in benign cells. Conversely, HNE immunostaining was strongest in invasive breast carcinomas (UDH versus invasive cohort, P = 0.015).
  
  
  CONCLUSIONS
  4-hydroxy-2-nonenal as a marker of lipid peroxidation increases during breast carcinogenesis, reflecting the role of oxidative stress in the pathogenesis of breast cancer. However, 8-OHdG shows diminished levels in carcinomas, possibly resulting from the induction of DNA repair in these invasive lesions.
authors.affiliation: Departments 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: Ulla
authors.initials: U
authors.lastname: Puistola
authors.forename: Arja
authors.initials: A
authors.lastname: Jukkola-Vuorinen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D045643:DNA Repair Enzymes / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000502:physiology; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D012189:Retrospective Studies
chemical_list: D000447:Aldehydes; D014408:Biomarkers, Tumor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045643:DNA Repair Enzymes; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal