Histopathology of familial ovarian tumors in women from families with and without germline BRCA1 mutations

Breast cancers from patients with germline BRCA1 mutations show characteris tic histopathologic features. However, similar studies of BRCA1-associated ovarian cancers have reported inconsistent findings. Interobserver differen ces in histopathologic classification are a significant source of variation , and most studies have obtained histopathologic information from pathology reports rather than from review of histopathology slides. We therefore rev iewed the histopathology slides and pathology reports to determine histolog ic type, grade, and stage for cancers of the ovary or peritoneum in 217 wom en from 126 families enrolled in the Gilda Radner Familial Ovarian Cancer R egistry. Peripheral blood DNA from at least 1 affected member of each famil y was analyzed for BRCA1 mutations, and tumors from BRCA1 mutation-positive families were compared with those from BRCA1-negative families. Of 66 pati ents from 56 BRCA1-positive families, 64 had ovarian carcinoma, 1 had an ov arian carcinoma in situ, and 1 had a dysgerminoma. Of 151 patients from 90 BRCA1-negative families, 135 had ovarian carcinoma, 10 had ovarian borderli ne tumors, 3 had ovarian sex cord/stromal tumors, and 3 had primary periton eal carcinoma. There were fewer grade 1 (P < .001) and stage I (P = .10) ca ncers in patients from BRCA1-positive families than in patients from BRCA1- negative families, Neither mucinous nor borderline tumors were found in the BRCA1-positive families. Ovarian cancers arising in women from BRCA1-posit ive families are more likely to be high grade and nommucinous than cancers arising in women from BRCA1-negative families. The absence of borderline tu mors in patients from BRCA1-positive families adds to accumulating evidence that BRCA1 mutations do not play a role in the development of these tumors . HUM PATHOL 31:1420-1424. Copyright (C) 2000 by W.B. Saunders Company.