title: Impact of the 2013 ASCO/CAP HER2 Guideline Updates at an Academic Medical Center That Performs Primary HER2 FISH Testing: Increase in Equivocal Results and Utility of Reflex Immunohistochemistry.
abstract: OBJECTIVE
  The 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline updates lowered the threshold for HER2 positivity and altered the equivocal category. The goal of this study was to evaluate the impact of these changes on the distribution of HER2 fluorescence in situ hybridization (FISH) status. The utility of reflex HER2 immunohistochemistry (IHC) for FISH equivocal cases was also examined.
  
  
  METHODS
  We retrospectively reviewed all invasive breast cancers analyzed for HER2 via dual-probe FISH (PathVysion; Abbott Laboratories. Abbott Park, IL) 12 months before and after the HER2 guidelines updates were implemented. Reflex HER2 IHC results were recorded for HER2 FISH equivocal cases.
  
  
  RESULTS
  There was a significant increase in the number of HER2 FISH equivocal results after the guideline updates (4.9% vs 1.4%, P = .0087) that was independent of specimen type (core vs surgical, P = .6). All 17 FISH equivocal cases after the updates had reflex HER2 IHC: two (12%) of 17 were positive, 12 (71%) of 17 remained equivocal, and three (18%) of 17 were negative.
  
  
  CONCLUSIONS
  Implementation of the 2013 ASCO/CAP HER2 guideline updates resulted in an increase in HER2 FISH equivocal results, which can be attributed to HER2 copy number, regardless of the HER2/CEP17 ratio. Reflex IHC for FISH equivocal cases is of limited utility; however, IHC does assign HER2 positivity or negativity in a small percentage of cases.
authors.affiliation: From Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, and Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Muller
authors.affiliation: From Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, and Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marotti
authors.affiliation: From Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, and Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Memoli
authors.affiliation: From Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, and Geisel School of Medicine at Dartmouth, Hanover, NH.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Wells
authors.affiliation: From Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, and Geisel School of Medicine at Dartmouth, Hanover, NH. Laura.J.Tafe@Hitchcock.org.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Tafe
mesh_terms: D000046:Academic Medical Centers; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D017410:Practice Guidelines as Topic / Q000592:standards*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor
keywords: ASCO/CAP HER2 guidelines; Breast cancer; HER2 FISH; HER2 IHC