DNA adduct 8-hydroxydeoxyguanosine, a novel putative marker of prognostic significance in ovarian carcinoma.
OBJECTIVE
Previous studies have suggested the importance of reactive oxygen species in all the steps of carcinogenesis. Antioxidant enzymes are considered as the most specific and efficient way to protect cells from reactive oxygen species. The purpose of the current study was to identify the role of oxidative stress and major antioxidant enzymes in ovarian carcinomas.


METHODS
The material consisted of 68 invasive ovarian carcinomas which were studied by immunohistochemistry with antibodies to antioxidant enzymes peroxiredoxins (Prxs) I-VI and thioredoxin and oxidative stress markers nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG). Both the intensity and the extent of the stainings were assessed, and the nuclear and cytoplasmic expressions were evaluated separately.


RESULTS
The study revealed the hydroxyl radical-derived oxidative stress marker in DNA, 8-OHdG, to be a powerful prognostic factor in ovarian carcinoma (Kaplan-Meier survival log-rank-analysis P = 0.003; risk of death to ovarian carcinoma 2.69; 95% confidence interval 1.35-5.35. 8-OHdG was also associated with poor differentiation (P = 0.053), higher stage (P < 0.001), and non-optimal surgical outcome (P = 0.002). High cytoplasmic Prx IV immunostaining was associated with a better prognosis (P = 0.024), and elevated cytoplasmic expression rates of Prxs V (P = 0.043) and VI (P = 0.032) were associated with a higher stage.


CONCLUSIONS
To conclude, it appears that hydroxyl radical-derived oxidative stress, but not nitric oxide radical-derived oxidative stress, plays a significant role in ovarian carcinogenesis. Immunohistochemical assessment of 8-OHdG could provide a useful prognostic marker in ovarian cancer.
Karihtala
Peeter
P
Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulo, Finland. peeter.karihtala@oulu.fi
Soini
Ylermi
Y
Vaskivuo
Liisa
L
Bloigu
Risto
R
Puistola
Ulla
U
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D000975:Antioxidants / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D018736:DNA Adducts / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D011379:Prognosis; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000975:Antioxidants; D014408:Biomarkers, Tumor; D018736:DNA Adducts; C002744:3-nitrotyrosine; D014443:Tyrosine; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine