3-nitrotyrosine and Ovarian-Neoplasms

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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adenocarcinoma, Mucinous; Antioxidants; Biomarkers, Tumor; Deoxyguanosine; Female; Humans; Immunohistochemistry; Neoplasm Proteins; Ovarian Neoplasms; Oxidative Stress; Peroxiredoxins; Reactive Oxygen Species; Thioredoxins; Tyrosine

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.. 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.. 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.. 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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antioxidants; Biomarkers, Tumor; Carcinoma; Cell Nucleus; Cytoplasm; DNA Adducts; Female; Guanine; Humans; Immunohistochemistry; Neoplasm Staging; Ovarian Neoplasms; Oxidative Stress; Prognosis; Survival Analysis; Tyrosine