BRCA1 Immunohistochemistry in a Genotypically Characterized Cohort.
Robert Soslow, Guangming Han, Karuna Garg, Marina Asher, Douglas Levine. Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Immunohistochemical evaluation for BRCA1 dysfunction is not in widespread clinical use. If validated, this may provide an efficient and low cost initial screen to select patients for targeted therapies, specifically, PARP inhibition. This methodology will also narrow the pool of patients who may benefit from screening for hereditary cancer syndromes and might provide prognostically relevant information.
Design: One section from each of 43 high grade serous ovarian carcinomas included in The Cancer Genome Atlas (TCGA) with known BRCA1 and BRCA2 status was evaluated with a commercially available monoclonal antibody against BRCA1 (clone MS110) after optimization and IRB approval. Genetic subgroups represented were: BRCA1 germline mutation; BRCA1 somatic mutation, BRCA1 promoter methylation; BRCA2 germline mutation; BRCA2 somatic mutation; BRCA unaffected. A semiquantitative estimate of the extent of tumor cell nuclear labeling was recorded and correlated with genetic status. Using a cutoff of 5% (negative versus positive) separated tumors into distinct groups.
Results: Negative results (loss of BRCA1 expression) were recorded in: all 4 BRCA1 germline mutants; 3/6 cases with BRCA1 somatic mutation; 11/13 cases with BRCA1 promoter methylation; 1/4 BRCA2 germline mutants; 0/4 BRCA2 somatic mutants; and 0/12 BRCA unaffected cases. Equivocal results, generally stemming from weak or absent internal positive controls, were recorded in every category but BRCA1 germine mutants, and totalled 6/43.
Conclusions: This study suggests that the use of a commercially available antibody against BRCA1 in a small series may have clinical utility.
Category: Gynecologic & Obstetrics
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 98, Tuesday Afternoon