Refining the Diagnostic Approach in the Evaluation of HER2 in Breast Cancer: A Survey of 2008 Invasive Breast Cancers Comparing a Rabbit Polyclonal Antibody, Rabbit Monoclonal Antibody with Fluorescence In Situ Hybridization
D Peker, RJ Poppiti, J Alexis, L Howard, E Saiz, H Yaziji. Mt. Sinai Medical Center, Miami Beach, FL; Vitro Molecular Laboratories, Miami, FL
Background: Currently, laboratory testing of HER-2 in breast cancer is the second most common predictive biomarker test performed worldwide. Yet, despite recent efforts to improve the accuracy of HER2 testing by regulatory bodies, this goal has not been accomplished. We wished to evaluate the potential utility of a recently-described HER2 rabbit monoclonal antibody alongside a well-established rabbit polyclonal antibody and a well-established FISH assay on a large cohort of breast cancers and correlate the results with FISH results as well as tumor histologic and nuclear grade.
Design: 2008 invasive breast cancer cases were included in this study. Tumors were tested with DAKO A0485 rabbit polyclonal antibody (also used in HercepTest; Dako, Carpenteria, CA, USA), rabbit monoclonal antibody (clone SP3; Thermo, Fremont, CA, USA), and an FDA-approved FISH assay (PathVysion; Abbott Molecular, DesPlaines, IL, USA). This study is a slight modification of a previously published QA program (JAMA 28;291(16):1972-7), where clinical testing for HER2 by FISH were paralleled by IHC testing as well as documentation of the Nottingham tumor grade and specifically the nuclear score.
Results: When FISH is considered the gold standard assay, the polyclonal antibody had a sensitivity of 100% and specifity of 78%, while SP3 showed 84% sensitivity and 93% specifity. While There was no significant correlation between Notthingham grade and HER-2 status, nuclear grade 1 had the most powerful (100%) negative predictive value of negative FISH results (p<0.001).
Conclusions: A few conclusions can be drawn from this study on a large cohort of patients: 1. While the recently described rabbit monoclonal antibody is more specific than the more established polyclonal antibody, it lacks from adequate sensitivity. 2. The combination of these two antibodies can accurately predict gene status by FISH and thus be considered an alternative to FISH testing to assess HER-2/neu status in patients with breast cancer. Even though using 2 antibodies for IHC testing will add to the cost of HER2 testing, it reduces the need to the much more expensive FISH test in the majority of cases. 2. FISH should remain mandatory for tumors with 2+ (equivalent) cases. 3. Tumors with nuclear grade 1 (regardless of histologic type) can be safely spared HER2 testing by either modality.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 59, Tuesday Morning