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JNCI Journal of the National Cancer Institute 1999 91(7):626-628; doi:10.1093/jnci/91.7.626
© 1999 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 91, No. 7, 626-628, April 7, 1999
© 1999 Oxford University Press


REPORTS

Comparison of Prophylactic Oophorectomy Specimens From Carriers and Noncarriers of a BRCA1 or BRCA2 Gene Mutation

John F. Stratton, C. Hilary Buckley, David Lowe, Bruce A. J. Ponder, the United Kingdom Coordinating Committee on Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group

Affiliations of authors: J. F. Stratton, Department of Obstetrics and Gynaecology, Rosie Maternity Hospital, Cambridge, U.K.; C. H. Buckley, Department of Reproductive Pathology, St. Mary's Hospital for Women and Children, Manchester, U.K.; D. Lowe, St. Bartholomew's Hospital, London, U.K.; B. A. J. Ponder, Department of Oncology, Addenbrooke's Hospital, Cambridge.

Correspondence to: Bruce A. J. Ponder, Ph.D., F.R.C.P., Cancer Research Campaign Department of Oncology, University of Cambridge, Cambridge Institute of Medical Research, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2XY, U.K.

BACKGROUND: The natural history of ovarian cancer is not well understood and, to date, there is conflicting evidence as to whether or not there is a demonstrable precursor lesion. Some women at high risk of developing ovarian cancer because of their family history elect to have a prophylactic oophorectomy. To determine whether or not a recognizable premalignant lesion could be defined in familial ovarian carcinogenesis, we reviewed ovarian tissue specimens from women whose ovaries were removed prophylactically before gene testing became available and who 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 the following four features: inclusion cysts, clefts and fissures, ovarian epithelial metaplasia, and the presence of papillae on the ovarian surface epithelium. The specimens were also examined closely for the presence of dysplasia and occult neoplasia. Furthermore, the occurrence of endometriosis and benign ovarian tumors was documented in these women. The protein truncation test, nonradioactive 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: Eleven women had inherited a mutated BRCA1 or BRCA2 gene; 26 women had not. There was no difference between these groups for any of the features studied. CONCLUSIONS: Our data suggest that many of the histologic "abnormalities" described in "normal" ovaries are, in fact, variations of the normal and are not associated with the development of cancer.



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