Histology of prophylactically removed ovaries from BRCA1 and BRCA2 mutation carriers compared with noncarriers in hereditary breast ovarian cancer syndrome kindreds.

The literature reports conflicting studies claiming premalignant histological features in benign ovaries from women who may have hereditary predilections for ovarian carcinoma. To test the veracity of these claims, this investigation studied ovaries prophylactically removed from members of hereditary breast ovarian cancer (HBOC) syndrome families who carry BRCA1 and BRCA2 mutations and compared these with the ovaries of mutation-negative women from the same HBOC syndrome kindred. Sixty cases of women from HBOC syndrome families who had undergone prophylactic oophorectomies and whose BRCA1 and BRCA2 mutation status had been tested were selected from our database. Thirty had tested positive for BRCA1 mutations, 3 carried BRCA2 mutations, and 27 were negative for both BRCA1 and BRCA2 germline mutations. Histologic material from each case was examined by light microscopy blinded to the mutation status. Histologic features, previously reported to be possible precursor lesions for ovarian cancer, were quantified. Data from BRCA1 and BRCA2 mutation carriers were compared with those from mutation-negative cases in the direct line of genetic inheritance from the same HBOC syndrome families. Statistical analysis found that a more frequent occurrence of ovarian surface micropapillae in 87% of mutation carriers compared with just 55% of mutation-negative cases was the only histologic feature which was significantly different between the two groups (P = 0.39). Cortical clefts tended to be deeper in the ovaries of mutation carriers, but this did not reach significance (P = 0.051). There were no other significant histologic differences between the ovaries removed from mutation carriers and those from noncarriers. The results of our large and prospectively controlled, blinded study contrast with those reported from smaller, unblinded investigations. Except for the possible biological significance of surface micropapillae on ovaries from BRCA1 and BRCA2 mutation carriers, we found no histologic evidence for a genetically determined ovarian carcinoma precursor lesion.

Casey MJ ，Bewtra C ，Hoehne LL ，Tatpati AD ，Lynch HT ，Watson P ... -  《GYNECOLOGIC ONCOLOGY》

Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations.

Casey MJ ，Synder C ，Bewtra C ，Narod SA ，Watson P ，Lynch HT ... -  《GYNECOLOGIC ONCOLOGY》

A high occurrence of BRCA1 and BRCA2 mutations among Czech hereditary breast and breast-ovarian cancer families.

Machácková E ，Foretová L ，Navrátilová M ，Valík D ，Claes K ，Messiaen L ... -  《-》

Frequency of BRCA1 and BRCA2 mutations in a clinic-based series of breast and ovarian cancer families.

Mutations in BRCA1 and BRCA2 account for a significant proportion of hereditary breast and ovarian cancer cases. In this study, we sought to determine the frequency of BRCA1- and BRCA2-mutation carrier families in a hospital-based cancer family registry. The frequency of families with germline truncating mutations in BRCA1 and BRCA2 was 17.3% (18/104) and 1.9% (2/104), respectively. Two novel truncating mutations, BRCA1 1848delGA and BRCA2 5694insT, were identified. We also sought to determine the carrier frequency of other affected family members for which the mutation lineage could be established within these families. Not including the probands, 72% (18/25) of the affected family members within the BRCA1 mutation-associated families were carriers, and all four affected members of the BRCA2 families were carriers. These data imply that risk evaluation based on cancer family history alone may result in inaccurate estimates, and where possible, mutation testing should be considered in other affected family members to verify carrier status.

Vaziri SA ，Krumroy LM ，Rostai M ，Casey G ... -  《-》

Expression of cell cycle regulatory proteins in ovaries prophylactically removed from Jewish Ashkenazi BRCA1 and BRCA2 mutation carriers: correlation with histopathology.

Kerner R ，Sabo E ，Gershoni-Baruch R ，Beck D ，Ben-Izhak O ... -  《GYNECOLOGIC ONCOLOGY》