Achieving 95% IHC/FISH Concordance for Her2: Causes and Implications of Discordant Cases
EE Grimm, RA Schmidt, PE Swanson, KH Allison. University of Washington Medical Center, Seattle, WA
Background: Her2 oncogene overexpression predicts treatment response to multiple therapies, most notably trastuzumab. ASCO-CAP consensus recommendations published in 2007 require Her2 IHC concordance with either a reference IHC sample or another validated Her2 assay, such as fluorescent in-situ hybridization (FISH). This benchmark dictated a higher concordance rate than many published articles report. While compiling concordance data at the University Of Washington Medical Center (UWMC), our concordance studies between IHC and FISH for 2007 showed >99% concordance on IHC 0/1+ cases and 96.5% concordance on IHC 3+ cases. We expanded our concordance studies to include cases from 3 consecutive years and investigated reasons for discordant cases.
Design: All cases having both IHC and FISH performed between 2005 and 2007 were analyzed. Discordant reported results were reviewed and patient histories were obtained when possible. IHC was performed using anti-Her2 antibody A0485 (Dako) and a home-brew procedure, with interpretation relying on 'subtraction' of the staining of non-neoplastic ducts from neoplastic ducts. FISH was performed using a validated commercial assay (Abbott-Vysis). When cancers were composed of subpopulations having different IHC and/or FISH expression, each subpopulation was treated as a separate case.
Results: From 2005-2007, 703 cases had both IHC and FISH studies performed. 14% were IHC positive, 31% were equivocal, and 54% were IHC negative. Overall concordance of IHC 0/1+ with FISH (-) was 98% (n= 364 cases) and with IHC 3+ and FISH (+) was 84% (n= 96 cases). Discordant cases included 15 that were IHC 3+, FISH (-). Of these, 9 would not have been interpreted as 3+ using the 2007 CAP/ASCO criteria; 2 others lacked internal controls. Hence, 2007 criteria improved concordance for IHC 3+ from 84% to 95%. Six other discordant cases were IHC 0/1+, FISH amplified (concordance for IHC 0/1+ is 99%). At least 2 of these patients were treated with trastuzumab before biopsy.
Conclusions: Overall concordance between IHC and FISH is high and ASCO/CAP criteria for IHC interpretation significantly improve concordance for IHC 3+ carcinomas. Even with revised criteria, discordant cases remain. Concordance is excellent for IHC 0/1+ FISH (-) cases and notably, some discordant cases in the latter group may relate to prior trastuzumab therapy. We propose that such cases be excluded from concordance studies.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 53, Tuesday Morning