Cell cycle and apoptotic proteins in relation to ovarian epithelial morphology

Abstract

Objective. To assess the relationship between the expression of cell cycle and apoptotic proteins and the morphological appearance of the surface epithelium in non-neoplastic ovaries. Methods. The subjects for this study were 79 women who had undergone oophorectomy for benign conditions at the North Middlesex Hospital, London, and Royal Free Hospital, London, and whose ovaries had been reported on routine histology as entirely normal or containing physiological cysts or endometriosis. The epithelial morphology was reassessed on haematoxylin and eosin-stained paraffin wax sections using nine cytological and architectural parameters associated with premalignant intraepithelial changes. A ‘score’ was obtained for each ovary. Expression of p53, Ki67, cyclin D1 and Bcl-2 in the surface, cystic and endometriotic epithelium was assessed in corresponding sections using standard immunohistochemistry. Results. The median score for the morphological changes was significantly higher in the sections, which expressed p53 compared to those which did not. This difference remained significant in a subanalysis of the sections, which did not contain endometriosis. No relationship was identified between the morphological score and the expression of Ki67, Bcl-2 and cyclin D1. Conclusion. Increased intraepithelial abnormality as assessed by an epithelial morphological score of ovarian sections is associated with expression of the p53 cell cycle protein. This lends credence to the hypothesis that the ovarian surface or cystic epithelium goes through an identifiable precursor or “premalignant” phase before the development of invasive disease. Further work is required to characterise the changes that take place before the development of malignancy in ovarian epithelium.