title: Breast carcinomas with borderline (2+) HER2 immunohistochemistry: percentage of cells with complete membrane staining for HER2 and the frequency of HER2 amplification.
abstract: OBJECTIVE
  HER2 status is vital for selecting breast cancer patients for trastuzumab treatment. One recommended approach is to assess immunohistochemical staining and then perform in situ hybridisation on those tumours with a borderline (2+) immunohistochemical result. This audit aimed to assess the value of the percentage of immunohistochemical staining in 2+ tumours in selecting tumours for in-situ hybridisation.
  
  
  METHODS
  HER2 immunohistochemistry and in situ hybridisation was performed according to UK guidelines. The percentage of complete membrane staining of invasive carcinoma cells for HER2 was recorded as part of routine reporting.
  
  
  RESULTS
  191 (11%) of 1735 invasive carcinomas were scored as 3+. 419 (24%) were scored as 2+. 57 of 413 2+ carcinomas (14%) were amplified (ratio of HER2 to chromosome 17 ≥ 2.0). The frequency of amplification was related to the percentage of complete membrane staining: eight of 149 (5%) with 10-19% membrane staining, 11 of 93 (12%) with 20-29% staining, 26 of 150 (17%) with 30-79% staining and 12 of 21 (57%) with 80-100% staining.
  
  
  CONCLUSIONS
  This audit suggests that increasing the threshold for 2+ from 10% to 20% complete membrane staining would reduce the number of in-situ hybridisation tests by 36%, but reduce the detection of amplified tumours by 14%.
authors.affiliation: Department of Histopathology, Nottingham University Hospitals, City Hospital Campus, Nottingham, UK. andrew.lee@nuh.nhs.uk
authors.forename: Andrew H S
authors.initials: AH
authors.lastname: Lee
authors.forename: Heather P
authors.initials: HP
authors.lastname: Key
authors.forename: Jane A
authors.initials: JA
authors.lastname: Bell
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Hodi
authors.forename: Ian O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases