title: Impact of an alternative chromosome 17 probe and the 2013 American Society of Clinical Oncology and College of American Pathologists guidelines on fluorescence in situ hybridization for the determination of HER2 gene amplification in breast cancer.
abstract: BACKGROUND
  The dual-probe fluorescence in situ hybridization (FISH) assay for human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer provides an HER2:CEP17 (centromere enumeration probe for chromosome 17) ratio. Copy number alteration (CNA) in CEP17 may skew this ratio. The authors analyzed the impact of the 2013 American Society of Oncology/College of American Pathologists (ASCO/CAP) guidelines and an alternative chromosome 17 probe on HER2 status in tumor specimens with CEP17 CNA.
  
  
  METHODS
  Specimens with CEP17 CNA (n = 310) were selected from 3048 tumor samples that were received from January 2013 to June 2015 for testing with the alternative chromosome 17 probe D17S122. Reclassification of HER2 status was assessed using the 2007 and 2013 ASCO/CAP guidelines.
  
  
  RESULTS
  The alternative chromosome 17 probe reclassified 82 of 310 (26.5%) and 87 of 310 (28.1%) tumors using the 2007 and 2013 guidelines, respectively. Of the 41 of 310 tumors (13.2%) that were reclassified from nonamplified to amplified according to 2007 guidelines, 28 of 41 (68.3%) had an average HER2 copy number ≥4.0 and <6.0. The 39 of 310 tumors (12.6%) that were reclassified from equivocal to amplified according to 2013 guidelines had a mean HER2 copy number between ≥4.0 and <6.0. Most of these patients had stage I, hormone receptor-positive, lymph node-negative tumors, which is an unusual clinicopathologic profile for HER2-amplified tumors, and most received HER2-targeted therapy in addition to endocrine therapy.
  
  
  CONCLUSIONS
  Reflex testing with an alternative chromosome 17 probe using the 2013 ASCO/CAP guidelines reclassified 28.1% of tumor samples that had CEP17 CNA, converting nearly one-half from equivocal to amplified. The benefit of HER2-targeted therapy in this patient population requires further study. Cancer 2017;123:2230-2239. © 2017 American Cancer Society.
authors.affiliation: Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Alana R
authors.initials: AR
authors.lastname: Donaldson
authors.affiliation: Department of Laboratory Medicine, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Shashirekha
authors.initials: S
authors.lastname: Shetty
authors.affiliation: Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Rivera
authors.affiliation: Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Bryce P
authors.initials: BP
authors.lastname: Portier
authors.affiliation: Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: G Thomas
authors.initials: GT
authors.lastname: Budd
authors.affiliation: Department of Pathology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah.
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.affiliation: Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Lanigan
authors.affiliation: Department of Pathology, Robert J. Tomsich Institute of Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Calhoun
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D002277:Carcinoma / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008495:Medical Oncology; D015335:Molecular Probes / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D010338:Pathology, Clinical; D017410:Practice Guidelines as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D015335:Molecular Probes; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: Erb-B2 receptor tyrosine kinase 2 (ERBB2); breast cancer; diagnosis; human epidermal growth factor receptor 2 (HER2); in situ hybridization; pathology; prognosis