Morphologic Patterns Associated with BRCA1 and BRCA2 Genotype.
Robert Soslow, Guangming Han, Narciso Olvera, Douglas Levine. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: It has been hypothesized that ovarian tumors with BRCA dysfunction might have a distinctive histologic appearance, often referred to as “BRCAness.” Data suggest that, like tumors with BRCA1 mutation, those showing solid and/or transitional cell-like features may be prognostically superior to other high grade serous carcinomas; and tumors with prominent infiltrating lymphocytes have been reported in the setting of BRCA dysfunction.
Design: The existence of BRCAness was studied by reviewing H&E slides from 43 high grade serous ovarian carcinomas, included in The Cancer Genome Atlas (TCGA), with known BRCA1 and BRCA2 status. Genetic subgroups represented were: BRCA1 germline mutation; BRCA1 somatic mutation, BRCA1 promoter methylation; BRCA2 germline mutation; BRCA2 somatic mutation; BRCA unaffected. Tumor architecture, tumor infiltrating lymphocytes (TILs), and the presence and extent of necrosis were recorded for each case. TILs were only evaluated in sections from the primary site (i.e. Fallopian tube or ovary). Histologic review was performed without knowlege of genotype.
Results: A combination of either solid or transitional cell-like architecture with tumor infiltrating lymphocytes was present in 13/31 cases (42%) with BRCA1 or BRCA2 abnormality, as compared with only 1/12 (8%) in the BRCA unaffected group. This phenotype was most commonly encountered in the BRCA1 promoter methylation group (7/13; 54%). None of the 4 BRCA1 somatic mutants showed this phenotype. TILs were found in 18/31 cases (58%) with BRCA1 or BRCA2 abnormality, as compared with only 2/12 (17%) in the BRCA unaffected group. TILs were found predominantly in cases with BRCA1 abnormality (16/23; 70%), including BRCA1 germline mutation (3/4). Geographic necrosis was also more common in cases with BRCA1 or BRCA2 abnormality (14/31; 45%) as compared with 2/12 (17%) in cases with intact BRCA1 and 2. Subgroups with the highest prevalence of geographic necrosis were BRCA1 germline mutants (3/4) and BRCA2 germline mutants (3/4).
Conclusions: BRCAness is not a specific trait, but it is characteristic of cases with BRCA1 and 2 dysfunction. Solid and transitional-cell like architecture, along with TILs and geographic necrosis are seen in significant numbers of these cases. None of these findings is specific for either BRCA1 or 2 germline mutation.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:15 AM
Platform Session: Section D, Monday Morning