title: Observer prediction of HER2 amplification in HercepTest 2+ breast cancers as a potential audit instrument.
abstract: OBJECTIVE
  Correct assignment of human epidermal growth factor receptor 2 (HER2) status in breast cancer is important. Indeterminate (2+) HER2 immunohistochemistry (IHC) is usually resolved by FISH for HER2 gene amplification. It was hypothesised that predicting HER2 amplification in IHC 2+ cases could improve audit of HER2 IHC and its interpretation.
  
  
  RESULTS
  One observer (J. J. G.) interpreted 4343 assessable HercepTests on consecutive breast cancers from the West of Scotland over 45 consecutive months during 2007-2010, with 2+ cases classified prospectively as 'probably amplified', 'possibly amplified' or 'probably not amplified' prior to FISH. A HER2 to chromosome 17 FISH ratio >2 was taken to define HER2 amplification. There were 265 3+ cases (6.1%) and 883 2+ cases (20.3%). Of 187 'probably amplified' 2+ cases, 166 (88.8%) were amplified, as were 90 (37.8%) of 238 'possibly amplified' 2+ cases. Of 458 'probably not amplified' but still 2+ cases, 59 (12.8%) were in fact amplified (overall χ2 333.89, df 2, P < 0.0001). In total, 580 of 4343 (13.4%) cancers were HER2-positive (265 3+ by IHC and 315 2+ and HER2 amplified).
  
  
  CONCLUSIONS
  Breast cancers HER2-indeterminate (2+) by HercepTest IHC can be strongly separated into those probably HER2 amplified, a core indeterminate group and those probably not HER2 amplified. The percentage of HER2 amplified cases in each category is proposed as an instrument for comparison of HER2 IHC and its interpretation between laboratories and observers.
authors: Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. going@udcf.gla.ac.uk
authors: James J
authors: JJ
authors: Going
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D003133:Commission on Professional and Hospital Activities; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases