title: Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France).
abstract: BACKGROUND
  Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment.
  
  
  OBJECTIVE
  We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP.
  
  
  METHODS
  IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples.
  
  
  RESULTS
  The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively.
  
  
  CONCLUSIONS
  This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.|Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/Inserm U1081, University of Nice Sophia Antipolis, Nice, France.
authors.forename: E
authors.initials: E
authors.lastname: Long
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.|Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/Inserm U1081, University of Nice Sophia Antipolis, Nice, France.
authors.forename: M
authors.initials: M
authors.lastname: Ilie
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.|Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/Inserm U1081, University of Nice Sophia Antipolis, Nice, France.
authors.forename: S
authors.initials: S
authors.lastname: Lassalle
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Butori
authors.affiliation: Department of Surgery, CLCC Antoine Lacassagne Center, Nice, France.
authors.forename: G
authors.initials: G
authors.lastname: Poissonnet
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.|Nice Hospital-Related Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors.forename: K
authors.initials: K
authors.lastname: Washetine
authors.affiliation: Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/Inserm U1081, University of Nice Sophia Antipolis, Nice, France.|Department of Thoracic Surgery, Pasteur Hospital, Nice, France.
authors.forename: J
authors.initials: J
authors.lastname: Mouroux
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.
authors.forename: V
authors.initials: V
authors.lastname: Lespinet
authors.affiliation: Department of Dermatology, Archet Hospital, Nice, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Lacour
authors.affiliation: INSERM UMR-S1147, Centre Universitaire des Saints-Pères, University Paris Sorbonne Cité, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Taly
authors.affiliation: INSERM UMR-S1147, Centre Universitaire des Saints-Pères, University Paris Sorbonne Cité, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Laurent-Puig
authors.affiliation: Department of Dermatology, Archet Hospital, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Bahadoran
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.|Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/Inserm U1081, University of Nice Sophia Antipolis, Nice, France.|Nice Hospital-Related Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors.forename: V
authors.initials: V
authors.lastname: Hofman
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice Cedex, France.|Institute for Research on Cancer and Aging, Nice (IRCAN) CNRS UMR 7284/Inserm U1081, University of Nice Sophia Antipolis, Nice, France.|Nice Hospital-Related Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors.forename: P
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003365:Costs and Cost Analysis; D005260:Female; D005602:France; D006801:Humans; D007150:Immunohistochemistry / Q000191:economics; D008545:Melanoma / Q000737:chemistry* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000032:analysis* / Q000235:genetics*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000191:economics / Q000379:methods; D012878:Skin Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf