title: Immunohistochemistry as a potential tool for routine detection of the NRAS Q61R mutation in patients with metastatic melanoma.
abstract: BACKGROUND
  It can be useful to assess the NRAS mutation status in patients with metastatic melanoma because NRAS-activating mutations confer resistance to RAF inhibitors, and NRAS-mutated patients appear to be sensitive to mitogen-activated protein kinase (MEK) inhibitors.
  
  
  OBJECTIVE
  We aimed to assess the diagnostic accuracy of an immunohistochemistry (IHC) approach using a novel anti-NRAS (Q61R) monoclonal antibody on formalin-fixed paraffin-embedded tissue samples from patients with metastatic melanoma.
  
  
  METHODS
  We conducted a retrospective multicenter cohort study on 170 patients with metastatic melanoma. The automated IHC assay was performed using the SP174 clone, and compared with results of the molecular testing.
  
  
  RESULTS
  Evaluation of a test cohort with knowledge of the mutation status established a specific IHC pattern for the mutation. In the independent blinded analysis of the remaining cases, the anti-NRAS (Q61R) antibody accurately identified all NRAS Q61R-mutated tumors, and demonstrated 100% sensitivity and specificity.
  
  
  CONCLUSIONS
  Limitations include retrospective design and lack of multicenter interobserver reproducibility.
  
  
  CONCLUSIONS
  The NRAS (Q61R) IHC assay is reliable and specific for the evaluation of the Q61R mutation status in metastatic melanoma and may be an alternative to molecular biology in evaluation of metastatic melanoma in routine practice.
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors: Marius
authors: M
authors: Ilie
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Elodie
authors: E
authors: Long-Mira
authors: EA4340-Biomarqueurs en Cancérologie et Onco-Hématologie (BCOH), University of Versailles Saint-Quentin-en-Yvelines (SQY), Boulogne, France; Department of General and Oncologic Dermatology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne, France.
authors: Elisa
authors: E
authors: Funck-Brentano
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Sandra
authors: S
authors: Lassalle
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Catherine
authors: C
authors: Butori
authors: Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors: Virginie
authors: V
authors: Lespinet-Fabre
authors: Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors: Olivier
authors: O
authors: Bordone
authors: Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors: Alexandre
authors: A
authors: Gay
authors: Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors: Katia
authors: K
authors: Zahaf
authors: Surgery Department, Comprehensive Cancer Center Antoine Lacassagne, Nice, France.
authors: Gilles
authors: G
authors: Poissonnet
authors: Dermatology Department, Archet II Hospital, Nice, France.
authors: Jean-Philippe
authors: JP
authors: Lacour
authors: Dermatology Department, Archet II Hospital, Nice, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Team 1, University of Nice Sophia Antipolis, Nice, France.
authors: Philippe
authors: P
authors: Bahadoran
authors: Institut National de la Santé et de la Recherche Médicale (INSERM) U1065, Team 1, University of Nice Sophia Antipolis, Nice, France.
authors: Robert
authors: R
authors: Ballotti
authors: Pathology and Molecular Biology Departments, Centre Hospitalier Universitaire (CHU) and EA2406 University of Bordeaux, Bordeaux, France.
authors: Audrey
authors: A
authors: Gros
authors: Department of Oncologic Dermatology, CHU Bordeaux, Bordeaux, France.
authors: Caroline
authors: C
authors: Dutriaux
authors: EA4340-Biomarqueurs en Cancérologie et Onco-Hématologie (BCOH), University of Versailles Saint-Quentin-en-Yvelines (SQY), Boulogne, France; Department of General and Oncologic Dermatology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne, France.
authors: Philippe
authors: P
authors: Saiag
authors: Pathology and Molecular Biology Departments, Centre Hospitalier Universitaire (CHU) and EA2406 University of Bordeaux, Bordeaux, France.
authors: Jean-Philippe
authors: JP
authors: Merlio
authors: Pathology and Molecular Biology Departments, Centre Hospitalier Universitaire (CHU) and EA2406 University of Bordeaux, Bordeaux, France.
authors: Béatrice
authors: B
authors: Vergier
authors: EA4340-Biomarqueurs en Cancérologie et Onco-Hématologie (BCOH), University of Versailles Saint-Quentin-en-Yvelines (SQY), Boulogne, France; Department of Pathology, Ambroise Paré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne, France.
authors: Jean François
authors: JF
authors: Emile
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France.
authors: Véronique
authors: V
authors: Hofman
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France; Human Biobank BB-0033-00025, Pasteur Hospital, Nice, France. Electronic address: hofman.p@chu-nice.fr.
authors: Paul
authors: P
authors: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015331:Cohort Studies; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis / Q000235:genetics*; D012189:Retrospective Studies; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: NRAS; Q61R mutation; SP174 clone; immunohistochemistry; metastatic melanoma; molecular biology