The significance of the alteration of 8-OHdG in serous ovarian carcinoma
نویسندگان
چکیده
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.
منابع مشابه
طبقهبندی مجدد کارسینوماهای سروز تخمدان با روش جدید تقسیمبندی دوگانه (two-tier) و بررسی بروز ژن P53 با رنگآمیزی ایمونوهیستوشیمی
Background: Recently the use of “two tier" grading system in which ovarian serous carcinoma was classified as low-grade or high-grade in comparing to preceding system has improved authority in prognosis and survival. This approach is simplistic, reproducible, and based on biologic evidence. In this study, we reclassified ovarian serous carcinoma by a new two-tier system for grading and then eva...
متن کاملPrognostic Values of Estrogen and Progesterone Expression Receptors in Ovarian Papillary Serous Carcinoma
Background and Objectives: Presence of steroid hormone receptors (estrogen and progesterone) in the tumor tissues of various organs correlates with response to therapy and prognosis. Since their role in ovarian cancer is still controversial, in this study we investigated the expression and prognostic value of the estrogen receptor (ER) and progesterone receptors (PR) in ovarian papillary ser...
متن کاملElevated 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 de...
متن کاملZosteriform metastasis of ovarian carcinoma
Distant metastases are rare during the course of ovarian carcinoma. Ovarian epithelial adenocarcinomas rarely metastasize to the skin which is seen in less than 4% of patients. It usually presents as subcutaneous nodules and, less commonly, as inflammatory metastases which mimic cellulitis or viral or bacterial skin infections. The histology in most of the tumours is grade 1 or 2 serous p...
متن کاملImmunohistochemical Characterization of Normal Ovary and Common Epithelial Ovarian Neoplasm with a Monoclonal Antibody to Cytokeratin and Vimentin
Background & Objective: The common epithelial ovarian tumors are classified into serous, mucinous, clear cell, endometrioid, the Brenner, mixed, and undifferentiated types. Cytoskeleton intermediate filament composition of ovarian tissues indicates that the cytokeratin and vimentin are observed in ovarian surface epithelium along with the common ovaria...
متن کامل