title: A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma.
abstract: BACKGROUND
  Determining the BRAF mutation status of patients with advanced metastatic melanoma is essential in order to assess patients' eligibility for targeted BRAF inhibitor therapy. The aim of this study was to validate the utility of immunohistochemistry (IHC) to rapidly obtain the BRAF status in the UK cancer centre setting.
  
  
  METHODS
  All samples sent for molecular testing for detection of the BRAF mutation over a 26-month period were prospectively tested using the VE1 monoclonal antibody IHC stain.
  
  
  RESULTS
  Two-hundred and nineteen samples from 214 patients were identified. All patients were AJCC stage III/IV, except one. There was an overall 95.0% (208/219) concordance rate, with a sensitivity of 94.4% (84/89) and a specificity of 95.4% (124/130) when using genomic assays as the gold standard. Discordance resulted from the inability of the molecular technique to detect the V600E2 mutation and an inability of the IHC staining technique to detect non-V600E mutations. Molecular testing on smaller tumour deposits was also unreliable.
  
  
  CONCLUSIONS
  IHC staining has good sensitivity and excellent specificity for BRAF V600E mutations. BRAF IHC can be incorporated into a BRAF mutation testing algorithm for UK cancer centres to as a feasible first-line assay and identify a subset of cases that require subsequent genomic testing. It has the additional major advantages of reduced cost and rapid turnaround time.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.
authors.forename: Michelle Chin I
authors.initials: MC
authors.lastname: Lo
authors.affiliation: Department of Histopathology (Box 235), Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Paterson
authors.affiliation: Department of Plastic and Reconstructive Surgery, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Maraka
authors.affiliation: Department of Plastic and Reconstructive Surgery, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Clark
authors.affiliation: Department of Cellular Pathology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.
authors.forename: Joseph
authors.initials: J
authors.lastname: Goodwill
authors.affiliation: Department of Clinical Oncology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.|Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Nobes
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.|Department of Dermatology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garioch
authors.affiliation: Department of Plastic and Reconstructive Surgery, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.|Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Moncrieff
authors.affiliation: Department of Histopathology (Box 235), Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK.
authors.forename: Ed
authors.initials: E
authors.lastname: Rytina
authors.affiliation: Department of Cellular Pathology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich NR4 7UY, UK.|Norwich Medical School, University of East Anglia, Norwich NR4 7TJ, UK.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Igali
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D005240:Feasibility Studies; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D006113:United Kingdom
chemical_list: D000911:Antibodies, Monoclonal; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf