Evaluation of HER2 fluorescent in-situ hybridization (FISH) status in 274 patients with invasive breast cancer: Comparison of the last 3 ASCO/CAP guidelines for fish interpretation and its effect on HER2 status classification

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Conference Proceeding

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Modern Pathology


Background: HER2 gene status as a primary predictor of responsiveness to HER2-targeted therapies in invasive breast carcinomas (IBC), is assessed by in situ hybridization (ISH) for HER2 gene amplification or protein overexpression assessed by immunohistochemistry (IHC). We sought to access the influence of changes in HER2 FISH ASCO /CAP reporting guidelines from 2007, 2013 and 2018 on HER2 status. Design: This is a retrospective study of patients with IBC, who underwent HER2FISH testing between 2006 and 2017. At our institution, HER2 status is first determined by HER2IHC staining. All the HER2IHC equivocal (2+) cases are reflexed to HER2FISH. HER2FISH status was assessed by using Vysis dual FISH probe (Abbott Molecular, Inc., FDA Approved PathVysion HER-2 DNA Probe Kit). A comparative analysis was made based on 2007, 2013 and 2018 ASCO/CAP guidelines to assess HER2 status reclassification. Results: Complete data were available on 274 patients with equivocal HER2IHC results, 104 (38%) Caucasians, 52 (19%) African American, 4(1%) other, and 114 (42%) unknown. The results are summarized in tables 1-3 below. (Table presented) Conclusions: We observed 27.2% reclassification rate by using 2013 guidelines compared to 2007, lower threshold for positive (from equivocal, 20.7% of patients re-classified to positive and 6.5% to negative HER2 status). In contrast, the 2018 updates eliminated the FISH equivocal category with concomitant Her2IHC correlation and additional scoring of tumor nuclei. Implementing 2018 CAP guidelines led to 100% reclassification of 2007 equivocal cases into in 81.7% negative cases and 18.3% positive for HER2 status. Prospective data on survival is necessary to evaluate impact of 2018 guidelines on outcomes.





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