Elevated serum 8-OHdG is associated with poor prognosis in epithelial ovarian cancer.

BACKGROUND: 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative stress in DNA. This study was undertaken to reveal whether serum 8-OHdG could be a prognostic factor in epithelial ovarian carcinoma (EOC). PATIENTS AND METHODS: Preoperative serum 8-OHdG levels were examined by enzyme-linked immunosorbent assay in 84 stage I-IV EOC patients. Immunohistochemical (IHC) 8-OHdG expression was determined in 78 of these patients. RESULTS: Strong 8-OHdG immunostaining predicted poor survival. High serum 8-OHdG (>140 pg/ml) was associated with poor ovarian cancer-specific survival (p<0.05) in patients with grade 1-2 EOC (p<0.05), but was not observed among the grade 3 patients. High 8-OHdG levels both in the serum and in the tumour tissue was associated with traditional factors of poor prognosis and serous histology. CONCLUSION: Both serum and IHC 8-OHdG assessment may serve as prognostic tools in EOC and the role of oxidative stress as a carcinogenic factor in ovarian cancer pathogenesis is also suggested.

Oxidative stress-induced antioxidant enzyme expression is an early phenomenon in ovarian carcinogenesis.

Oxidative stress and antioxidant enzymes have been widely investigated in various carcinomas. However, there is only some information about their role in ovarian carcinogenesis or in ovarian carcinomas in vivo. We studied immunohistochemical nuclear and/or cytoplasmic expression of oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine, as well as major antioxidative enzymes peroxiredoxins (PRDX) I-VI and thioredoxin (TXN) in ovarian tumours. The material consisted of 20 benign (10 serous, 10 mucinous) and 51 borderline (33 serous, 18 mucinous) epithelial ovarian tumours. The markers of oxidative stress, 8-OHdG and nitrotyrosine, were seen already in benign tumours (in 20% and 45% of the tumours, respectively) and their expression patterns were similar in benign and borderline tumours. The levels of PRDX II, III, IV, V and VI were significantly higher in borderline than in benign tumours (p<0.02 for all). Specifically for PRDX II (for both nuclear and cytoplasmic expression, p<0.00005) and PRDX VI (for cytoplasmic expression, p=0.0003 and for nuclear expression, p=0.0005) the difference between benign and borderline tumours was remarkable. In general, serous benign and borderline tumours expressed higher antioxidant enzyme levels than mucinous ones. Nuclear TXN was expressed more strongly in benign than in borderline tumours (p=0.003). Oxidative stress occurs already in benign ovarian tumours and the levels are comparable to borderline tumours. However, some of the antioxidant enzymes, especially PRDX II and VI, are more profoundly induced in borderline ovarian tumours, reflecting their possible role as cancer preventers. This difference could also offer a potential tool for differential diagnosis between benign and borderline epithelial ovarian tumours.