Adherence to ASCO/CAP HER2 Testing Guidelines: Equivocal Rates and Impact on Management within a Single Institution.
Bryce P Portier, Erinn Downs-Kelly, Chris Lanigan, Claudiu Cotta, Deepa Patil, Gary Procop, James R Cook, Halle Moore, George T Budd, Raymond R Tubbs. Cleveland Clinic, OH; Taussig Cancer Institute, Cleveland, OH
Background: The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 guidelines utilize immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) algorithms to improve HER2 testing. Our aim was to evaluate adherence to ASCO/CAP guidelines within a single institution performing a high volume of HER2 testing, to assess the ability of the guidelines to resolve equivocal results, and to assess the impact of unresolved equivocal HER2 results on patient management.
Design: All patients (1,770) with breast carcinoma tested for HER2 within the Cleveland Clinic system from January 2008 to June 2010 were included. HER2 status and clinicopathologic data (age, tumor grade and stage, hormone receptor status, HER2/CEP17 ratio, and treatment) was retrieved from the electronic medical record. The primary method of HER2 testing at our institution is a dual probe FISH assay (PathVysion, Abbott-Vysis, Chicago, IL) with reflex testing of equivocal cases by HER2 IHC (PATHWAY anti-HER2/neu, Ventana, Tucson, AZ).
Results: A total 1,770 cases were analyzed by FISH over the study period; 79 (4.4%) were identified as equivocal. All 79 were rescored by a second technologist and then reflex tested via IHC (100% ASCO/CAP compliance). IHC resolved the equivocal status in 55 (70%) patients, with 12 (15%) identified as positive (3+) and 43 (55%) as negative (0 or 1+). A double equivocal result by both FISH and IHC was seen in 24 (30%) cases. Within this double equivocal group, 6 patients (25%) received Trastuzumab (Herceptin; Genentech, South San Francisco, CA). The only statistically significant clinicopathologic factor in patients that were treated with Herceptin was age <50 (p = 0.003).
Conclusions: Previous literature has shown that employing FISH rather than IHC as the primary HER2 testing methodology results in fewer equivocal cases (5% versus 32%, respectively Grimm et al 2010); our current study shows a similar equivocal rate (4.4%) by primary FISH. Reflex HER2 IHC testing resolved 70% of the equivocal FISH cases, however 30% were equivocal by both methodologies. These double equivocal cases are problematic in that there is no accepted guideline for the management of these patients. Outcome studies with long-term follow-up are needed to establish an optimal management plan for the double equviocal subset of breast cancer patients.
Category: Quality Assurance
Monday, February 28, 2011 1:00 PM
Poster Session II # 208, Monday Afternoon