title: Image analysis as an adjunct to manual HER-2 immunohistochemical review: a diagnostic tool to standardize interpretation.
abstract: OBJECTIVE
  Accurate determination of HER-2 status is critical to identify patients for whom trastuzumab treatment will be of benefit. Although the recommended primary method of evaluation is immunohistochemistry, numerous reports of variability in interpretation have raised uncertainty about the reliability of results. Recent guidelines have suggested that image analysis could be an effective tool for achieving consistent interpretation, and this study aimed to assess whether this technology has potential as a diagnostic support tool.
  
  
  RESULTS
  Across a cohort of 275 cases, image analysis could accurately classify HER-2 status, with 91% agreement between computer-aided classification and the pathology review. Assessment of the continuity of membranous immunoreactivity in addition to intensity of reactivity was critical to distinguish between negative and equivocal cases and enabled image analysis to report a lower referral rate of cases for confirmatory fluorescence in situ hybridization (FISH) testing. An excellent concordance rate of 95% was observed between FISH and the automated review across 136 informative cases.
  
  
  CONCLUSIONS
  This study has validated that image analysis can robustly and accurately evaluate HER-2 status in immunohistochemically stained tissue. Based on these findings, image analysis has great potential as a diagnostic support tool for pathologists and biomedical scientists, and may significantly improve the standardization of HER-2 testing by providing a quantitative reference method for interpretation.
authors.affiliation: SlidePath Ltd., Swift Square, Northwood Business Park, Santry, Dublin 9, Ireland. lynne.dobson@slidepath.com
authors.forename: Lynne
authors.initials: L
authors.lastname: Dobson
authors.forename: Catherine
authors.initials: C
authors.lastname: Conway
authors.forename: Alan
authors.initials: A
authors.lastname: Hanley
authors.forename: Alex
authors.initials: A
authors.lastname: Johnson
authors.forename: Sean
authors.initials: S
authors.lastname: Costello
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Grady
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Connolly
authors.forename: Hilary
authors.initials: H
authors.lastname: Magee
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Shea
authors.forename: Michael
authors.initials: M
authors.lastname: Jeffers
authors.forename: Elaine
authors.initials: E
authors.lastname: Kay
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D015331:Cohort Studies; D003936:Diagnosis, Computer-Assisted; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods* / Q000592:standards; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human