title: ALK Immunohistochemistry in NSCLC: Discordant Staining Can Impact Patient Treatment Regimen.
abstract: Diagnostic immunohistochemistry (IHC) is increasingly accepted as a screening method for anaplastic lymphoma receptor tyrosine kinase gene (ALK) rearrangements in NSCLC. We have sought to establish an ongoing robust external quality assessment process to gauge quality of anaplastic lymphoma kinase (ALK) IHC, which can have an impact on interpretation of patient samples.
  
  
  
  Unstained tissue and cell line samples were distributed on a quarterly basis to participating laboratories from 30 countries. Participants stained the slide using their routine diagnostic ALK IHC method and returned the slide along with their in-house control and methodology details. Slides were assessed by a team of pathologists and scientists.
  
  
  
  Overall, there was a mean pass rate of 83% (range 71%-98%), with 38 variations in staining protocol. Methods included the following: the Roche D5F3 assay (65% of users, pass rate 93%); Novocastra 5A4 (15% of users, pass rate 65%); Cell Signaling Technology D5F3 (7% of users, pass rate 91%), and Dako ALK1 (5% of users, pass rate 50%). Choice of methodology directly affected final interpretation of distributed ALK-positive and ALK-negative NSCLC cases, which were correctly identified by 89% and 88% of participants, respectively. Antibody detection method was a contributing factor in false-negative staining results. The choice of laboratory controls was found to be unsuitable, and as such, in-house control recommendations are also provided.
  
  
  
  ALK IHC is a robust screening technique, but there is concern that some diagnostic laboratories are using inadequate staining methods, which has a direct impact on final interpretation. External assessment helps provide laboratories with continued confidence in their ALK IHC testing.
authors.affiliation: U.K. National External Quality Assessment Scheme Immunocytochemistry and In Situ Hybridisation, University College London Cancer Institute, Research Department of Pathology, University College London, United Kingdom. Electronic address: merdol.ibrahim@ucl.ac.uk.
authors.forename: Merdol
authors.initials: M
authors.lastname: Ibrahim
authors.affiliation: U.K. National External Quality Assessment Scheme Immunocytochemistry and In Situ Hybridisation, University College London Cancer Institute, Research Department of Pathology, University College London, United Kingdom.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Parry
authors.affiliation: U.K. National External Quality Assessment Scheme Immunocytochemistry and In Situ Hybridisation, University College London Cancer Institute, Research Department of Pathology, University College London, United Kingdom.
authors.forename: Dawn
authors.initials: D
authors.lastname: Wilkinson
authors.affiliation: U.K. National External Quality Assessment Scheme Immunocytochemistry and In Situ Hybridisation, University College London Cancer Institute, Research Department of Pathology, University College London, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Bilbe
authors.affiliation: University College London Advanced Diagnostics, Research Department of Pathology, University College London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Allen
authors.affiliation: Royal Liverpool University Hospital, Liverpool, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Forrest
authors.affiliation: Northern Ireland Molecular Pathology Laboratory, Belfast Health and Social Care Trust and Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: Perry
authors.initials: P
authors.lastname: Maxwell
authors.affiliation: Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Grady
authors.affiliation: Birmingham Heartlands Hospital, Birmingham, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Starczynski
authors.affiliation: Queen Elizabeth Hospital, Birmingham, United Kingdom.
authors.forename: Philippe
authors.initials: P
authors.lastname: Tanier
authors.affiliation: Royal Liverpool University Hospital, Liverpool, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Gosney
authors.affiliation: Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Kerr
authors.affiliation: U.K. National External Quality Assessment Scheme Immunocytochemistry and In Situ Hybridisation, University College London Cancer Institute, Research Department of Pathology, University College London, United Kingdom.
authors.forename: Keith
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Thunnissen
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK IHC; External quality assessment; Immunohistochemistry; NSCLC