The natural history of ovarian cancer is not well understood and, to date, thereis conflicting evidence as to whether or not there is a demonstrable precursor lesion. Somewomen at high risk of developing ovarian cancer because of their family history elect to have aprophylactic oophorectomy. To determine whether or not a recognizable premalignant lesioncould be defined in familial ovarian carcinogenesis, we reviewed ovarian tissue specimens fromwomen whose ovaries were removed prophylactically before gene testing became available andwho were tested subsequently for BRCA1 or BRCA2 gene mutations.Methods
We analyzed ovarian tissue specimens from 37 women. The specimens were examined for the presence of thefollowing four features: inclusion cysts, clefts and fissures, ovarian epithelial metaplasia, and thepresence of papillae on the ovarian surface epithelium. The specimens were also examinedclosely for the presence of dysplasia and occult neoplasia. Furthermore, the occurrence ofendometriosis and benign ovarian tumors was documented in these women. The proteintruncation test, nonradioactive single-stranded conformation polymorphism analysis, andheteroduplex analysis, followed by DNA sequencing, were used to identify BRCA1 or BRCA2mutations in either blood samples or ovarian tissue specimens.Results
Eleven women hadinherited a mutated BRCA1 or BRCA2 gene; 26 women had not. There was no differencebetween these groups for any of the features studied.Conclusions
Our data suggest thatmany of the histologic “abnormalities” described in “normal”ovaries are, in fact, variations of the normal and are not associated with the development ofcancer.