Prophylactic oophorectomy: a morphologic and immunohistochemical study

BACKGROUND: The tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium. METHODS: Morphologic features and immunohistochemical expression patterns of CA-125, Ki-67, p53, E-cadherin, and Bcl-2 were evaluated in 21 normal ovaries, 31 ovaries that were removed prophylactically for increased carcinoma risk, and 7 ovarian papillary serous carcinomas. Representative slides from formalin-fixed, paraffin-embedded tissue blocks were submitted to immunohistochemical staining and were evaluated independently by three gynecologic pathologists. For statistical analyses, Fisher exact tests, multivariate analyses, Spearman rank correlation coefficients, Wald statistics, Kruskal-Wallis tests, and Mann-Whitney tests were used. Immunohistochemical staining results were correlated with morphologic findings. RESULTS: The authors found progressive increases in reactivity with the lowest expression in normal ovarian epithelium, stronger expression in epithelium from prophylactically removed ovaries, and the highest expression in carcinomas for Ki-67 and p53. A similar trend was observed for CA-125. Positivity for Ki-67 and p53 was seen predominantly in the epithelium of inclusion cysts and deep invaginations, including those areas that had been identified as hyperplastic or dysplastic on routine hematoxylin and eosin-stained sections. CONCLUSIONS: The current results suggest biologic/molecular evidence for the existence of preneoplastic changes in ovarian surface epithelium and support the previously proposed concept of ovarian dysplasia. Subtle morphologic alterations of the ovarian epithelium may be biologically significant.