BRCA Dysfunction in Ovarian Tumor Cannot Be Reliably Predicted by Morphology.
Guangming Han, Karuna Garg, Blake Gilks, Robert A Soslow. University of Calgary/Calgary Laboratory Services, AB, Canada; Memorial Sloan-Kettering Cancer Center, New York; Vancouver General Hospital, BC, Canada
Background: Anecdotal data suggests that ovarian tumors with BRCA abnormalities often show tumor infiltrating lymphocytes (TILs), and solid or transitional cell-like growth pattern. This study examines the possibility of predicting BRCA dysfunction (“BRCAness”) based on the presence of these morphologic features.
Design: A consecutive series of 44 ovarian carcinomas were reviewed for tumor subtype, presence of TILs, solid or transitional cell-like growth pattern, and geographic necrosis, without knowledge of BRCA1 and BRCA2 status. TILs were only evaluated in sections from the primary tumor. A prediction of possible BRCA dysfunction was made when a combination of two or more of the above features were present in a high grade serous carcinoma (HSC). The predicted status was then correlated with the actual BRCA1/2 status.
Results: Among the HSCs, morphologic prediction of possible BRCA dysfunction was made on 7/10 cases with (70%) BRCA1 or 2 germline or somatic mutation, 9/10 (90%) cases with BRCA1 promoter methylation, and 8/15 (53%) cases without BRCA mutation or methylation (no BRCA loss group). All 9 cases of non-HSCs were predicted as no BRCA dysfunction and did not show BRCA mutation or methylation. There were significantly more BRCA mutation or promoter methylation cases in the predicted BRCA dysfunction group than in the predicted no BRCA dysfunction group (p = 0.002) when considering all cases. However, this difference was not significant when only HSCs were considered (p = 0.095). Within the HSC subtype, TILs were more frequently present in the BRCA1 promoter methylation group (9/10, 90%) compared to other groups (4/10 in BRCA1 or 2 mutation group, 7/15 in no BRCA loss group) (p = 0.015). Transitional-like morphology was more frequently present in the BRCA1 or 2 mutation group (8/10, 80%) compared to the BRCA1 promoter methylation group (4/10) and no BRCA loss group (6/15) (p = 0.037). There was no significant difference in the presence of solid growth pattern or geographic necrosis among the subgroups.
Conclusions: TILs and/or transitional-like growth pattern are seen in the majority of cases with BRCA1 or 2 dysfunction, especially in the BRCA1 promoter methylation group. However, there is tremendous morphologic overlap between tumors with and without BRCA dysfunction. While HSC subtype remains a useful indicator for potential BRCA screening, we cannot, at this point, reliably predict subsets of HSC with BRCA abnormalities based solely on morphologic features.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 97, Tuesday Afternoon