The significance of the alteration of 8-OHdG in serous ovarian carcinoma.

BACKGROUND

Oxidative damage and DNA repair dysfunction are associated with carcinogenesis. 8-OHdG is one of the major oxidative DNA adducts. Present work aims to investigate whether the expression of 8-OHdG and its key repair gene hOGG1 play distinctive role in two types of serous ovarian cancer.

MATERIALS AND METHODS

8-OHdG level in DNA from tumor and matched tumor-adjacent normal tissue in 48 high-grade papillary serous carcinomas (HG-SOC), 24 low-grade papillary serous carcinomas (LG-SOC), 20 serous cystadenomas, and 16 non-tumor control ovaries was tested. The Cox proportional hazards model and the log-rank test were used to assess the associations between the 8-OHdG level in two types of serous cancer and patients' survival. Real-time polymerase chain reaction and protein immunoblot were employed to detect hOGG1 mRNA and protein levels in tumor and adjacent normal tissues. Immunohistochemistry was used to determine the expression of hOGG1 and p53.

RESULTS

There was no difference of average 8-OHdG/106dG DNA level either between HG-SOC (27.8 ± 8.9), LG-SOC (25.2 ± 7.4) and benign serous cystadenoma (26.5 ± 7.7, p = 0.35); or between the tumor-adjacent normal tissue of HG-SOC (18.8 ± 5.2), LG-SOC (21.4 ± 6.5), benign serous cystadenoma (20.5 ± 9.1) and non-tumor ovary (21.6 ± 4.9, p = 0.62). The 8-OHdG/106dG level was significantly higher in tumor comparing to that in matched normal tissue adjacent to carcinoma in HG-SOC (1.52 ± 0.52, p = 0.02), but not in LG-SOC or benign serous cystadenoma. Increased level of 8-OHdG in tumor DNA was an independent factor of overall survival in serous ovarian carcinoma upon multivariate analysis (p < 0.01). Increased level of 8-OHdG in tumor DNA indicates poorer overall and progression-free survival durations than counterparts (47.3 vs 105.7 months and 13.5 vs 45.3 months, respectively). Protein levels of hOGG1 were remarkably decreased in HG-SOC (p < 0.01), but not in LG-SOC and serous cystadenoma compared with the tissue adjacent to carcinoma. A positive result on p53 immunostaining was associated with lower hOGG1 expression in HG-SOC (p = 0.04).

CONCLUSION

Increased 8-OHdG level and decreased expression of hOGG1 in tumor were found in HG-SOC but not LG-SOC. Increased 8-OHdG level in tumor DNA was significantly associated with poorer overall survival and progression-free survival in serous ovarian carcinoma.