title: HER2 FISH classification of equivocal HER2 IHC breast cancers with use of the 2013 ASCO/CAP practice guideline.
abstract: The status of human epidermal growth factor receptor 2 (HER2, ERBB2) determines the eligibility of breast cancer patients to receive HER2-targeted therapy. The majority of HER2 testing in the U.S. is performed using a combination of immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH) for IHC equivocal cases. In 2013, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) updated the guideline for HER2 testing. This study evaluates the impact of the 2013 ASCO/CAP updated guideline on final HER2 FISH classification of breast cancers with an equivocal IHC result. For each case, we reported a FISH result according to the 2013 updated guideline and recorded a separated result using the 2007 guideline for investigational purpose. McNemar's test and Bowker's symmetry test were used to compare the classifications by the two guidelines. Among 172 HER2 IHC 2+ equivocal cases, use of the 2103 guideline changed classifications in 36 cases (21 %) when compared with the results expected by use of the 2007 guideline, and yielded a higher proportion of positive (28.5 vs. 23.3 %) and equivocal (16.3 vs. 4.1 %), and a lower proportion of negative (55.2 vs. 72.7 %) cases (p < 0.001). The major classification change with use of the updated guideline is from the HER2 FISH negative to equivocal in 26 cases (15 %). Our study has shown that implementation of the 2013 ASCO/CAP updated guideline has significant impact on HER2 classification for breast cancers with an equivocal HER2 IHC result and therefore increased the use of HER2-targeted therapy. Our data have also shown that reflex FISH is effective for final classification of the IHC equivocal cases and that polysomy 17 (CEP17 copy number ≥3/cell) is present in a significantly higher proportion of cases with an equivocal HER2 FISH classification.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA. yfan@med.miami.edu.
authors.forename: Yao-Shan
authors.initials: YS
authors.lastname: Fan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Casas
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Watkins
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chapman
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Offiong Francis
authors.initials: OF
authors.lastname: Ikpatt
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, 1601 NW 12th Avenue, Rm 7050, Miami, FL, 33136, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gomez
authors.affiliation: Biostatistics and Bioinformatics Core Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.|Biostatistics and Bioinformatics Core Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL, USA.
authors.forename: Isildinha M
authors.initials: IM
authors.lastname: Reis
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: ASCO/CAP practice guideline; Breast cancer; Fluorescence in situ hybridization; HER2; Immunohistochemistry; Polysomy 17