Comparison of prophylactic oophorectomy specimens from carriers and noncarriers of a BRCA1 or BRCA2 gene mutation

Background: The natural history of ovarian cancer is not well understood an d, to date, there is conflicting evidence as to whether or not there is a d emonstrable precursor lesion, Some women at high risk of developing ovarian cancer because of their family history elect to have a prophylactic oophor ectomy, To determine whether or not a recognizable premalignant lesion coul d be defined in familial ovarian carcinogenesis, we reviewed ovarian tissue specimens from women whose ovaries were removed prophylactically before ge ne testing became available and who were tested subsequently for BRCA1 or B RCA2 gene mutations. Methods: We analyzed ovarian tissue specimens from 37 women, The specimens were examined for the presence of the following four f eatures: inclusion cysts, clefts and fissures, ovarian epithelial metaplasi a, and the presence of papillae on the ovarian surface epithelium, The spec imens were also examined closely for tbe presence of dysplasia and occult n eoplasia, Furthermore, the occurrence of endometriosis and benign ovarian t umors was documented in these women, The protein truncation test, nonradioa ctive single-stranded conformation polymorphism analysis, and heteroduplex analysis, followed by DNA sequencing, were used to identify BRCA1 or BRCA2 mutations in either blood samples or ovarian tissue specimens. Results: Ele ven women had inherited a mutated BRCA1 or BRCA2 gene; 26 women had not, Th ere was no difference between een these groups for any of the features stud ied, Conclusions: Our data suggest that many of the histologic "abnormaliti es" described in "normal" ovaries are, in fact, variations of the normal an d are not associated with the development of cancer.