---------------------------- 2011 Platform Presentation Winner --------------------------

[1043] Germline BRCA1 Mutation Positive Ovarian Cancer Exhibits a Distinctive Highly Specific Phenotype.

Mika Fujiwara, Anna Felberg, Alice S Whittemore, Valerie M McGuire, Teri A Longacre. Stanford University School of Medicine, CA

Background: Patients with BRCA1 germline mutation are at increased risk of developing both breast and ovarian cancer. BRCA1 breast cancer is associated with specific tumor morphology, but, other than high grade serous histology, specific histologic features of the ovarian tumors in these patients have not been described. We investigated whether BRCA1 ovarian cancer demonstrate characteristic histologic findings that are predictive of BRCA1 status.

Design: We reviewed the pathologic features of 326 ovarian cancers with known germline BRCA1 mutational status from a population-based ovarian cancer registry. Tumors were evaluated independent of BRCA mutational analysis and classified into 2 categories: “Not compatible with BRCA1” and “Compatible with BRCA1” on the basis of the following criteria: serous/undifferentiated vs. other histology; marked vs. minimal to moderate atypia; abundant mitotic figures vs. few or scattered mitoses; giant, bizarre nuclei vs. monomorphic nuclei; and prominent intraepithelial lymphocytes vs. few or no lymphocytes. Tumors that showed only 2 of these features were separately classified as “Possibly compatible with BRCA1.” Tumors that demonstrated “Compatible with BRCA1” histology were additionally investigated for presence/absence of a dominant mass, fallopian tube mucosal involvement, and uterine cornu involvement. Results were correlated with germline BRCA1 status.

Results: 326 ovarian tumors (28/326 [8.6%] BRCA1 positive and 298/326 [91.4%] BRCA1 negative) were reviewed and classified as follows: 240/326 (73.6%) “Not compatible”, 44/326 (13.5%) “Possibly compatible”; and 42/326(12.9%) “Compatible.” Germline BRCA1 mutations were present in 3.8% “Not compatible” and 26.2% “Compatible.” The sensitivity and specificity of “Compatible” morphology were 55.0% and 88.2%, respectively; while the sensitivity and specificity of combined “Compatible” and “Possibly compatible” morphology were 67.9% and 77.5%, respectively. The presence/absence of a dominant mass, fallopian tube mucosal involvement, and uterine cornu involvement did not predict BRCA1 status.

Conclusions: A combination of serous/undifferentiated histology, marked nuclear atypia, high mitotic index, giant, bizarre nuclei and prominent intraepithelial lymphocytes appears to be highly specific for germline BRCA1 mutation positive ovarian cancer (negative predictive value >95%) in this catchment area. Ovarian tumor specific histology may help identify women for BRCA1 mutational analysis in the appropriate clinical setting.
Category: Gynecologic & Obstetrics

Monday, February 28, 2011 11:00 AM

Platform Session: Section D, Monday Morning, United States and Canadian Academy of Pathology