Studies to investigate a possible association between Polycystic Ovary Syndrome and Epithelial Ovarian Cancer

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders, affecting 5 % to 10 % of women of reproductive age. The Syndrome is associated with Type II diabetes and endometrial carcinoma but an association with epithelial ovarian cancer has also been suggested. The studies described in this thesis were designed to investigate this association at population, cellular and molecular levels. In the first study, a cross sectional questionnaire survey was conducted of 121 women aged between the ages of 20 and 40, with or without PCOS. Analysis of the replies from 52 women with PCOS and 82 controls, showed that women with PCOS were significantly more likely to give a positive family history of breast cancer and myocardial infarction (20% vs 5%, p<0.05 and 35% vs 15%, p, 0.05, respectively). The second study was performed on 102 formalin fixed, paraffin embedded ovarian biopsies. In this study the surface epithelium of PCOS ovaries was compared with controls. The results showed significant epithelial changes in the PCOS group, with a higher prevalence of Psammoma bodies and mitoses (p< 0.01 and p < 0.02, respectively). Expression of cell cycle and apoptotic (p53, Cyclin D, Ki67 and bcl2) proteins in the ovarian surface epithelium was assessed using immunohistochemistry in 15 PCOS subjects and 15 controls. P53 expression was significantly (p= 0.003) increased in the PCOS women compared with controls. The third project was performed to identify gene expression in ovaries from women with PCOS, ovarian cancer and healthy controls (three ovaries from each group were utilized). 34(2%) genes consistently varied in abundance between normal and PCOS samples, 12 genes were over expressed in PCOS and 22 under expressed. One of the over expressed genes identified is human alpha 2 smooth muscle actin. It was 15 fold higher in PCOS ovary, than in normal ovary p< 0.001. Conclusions: the results of these studies do not provide convincing evidence of a correlation between PCOS and ovarian cancer.