title: BRAFp.V600E, p.V600K, and p.V600R Mutations in Malignant Melanoma: Do They Also Differ in Immunohistochemical Assessment and Clinical Features?
abstract: BACKGROUND
  Although the detection of BRAF p.V600E mutation by immunohistochemistry was clearly described in melanoma, discordant evidences were reported for the detection of p.V600K and p.V600R mutations. The aim of the study was to evaluate the efficacy of BRAFp.V600E, p.V600K, and p.V600R detection by immunohistochemistry in melanoma.
  
  
  METHODS
  Immunohistochemistry with VE1 antibody was performed on 18 tissue samples of metastatic melanomas with known BRAF mutational status.
  
  
  RESULTS
  The concordance rate of immunohistochemistry was 100% for p.V600E mutation. In contrast, the 7 p.V600K-mutated melanomas were scored as negative. p.V600K-mutated melanomas were significantly associated with older age, male sex, and worst clinical outcome.
  
  
  CONCLUSIONS
  Immunohistochemistry could efficaciously be adopted as a first step for the detection of BRAFp.V600E mutation in the initial selection of patients with advanced melanomas as candidates for BRAF inhibitors. It should be followed by molecular techniques in p.V600E-negative melanomas, for the specific search of p.V600K and other non-p.V600E BRAF mutations.
authors.affiliation: Departments of *Clinical and Diagnostic Medicine and Public Health †Pathology ‡Dermatology §Oncology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Aldo
authors.initials: A
authors.lastname: Tomasi
authors.forename: Antonio
authors.initials: A
authors.lastname: Maiorana
authors.forename: Cristel
authors.initials: C
authors.lastname: Ruini
authors.forename: Monia
authors.initials: M
authors.lastname: Maccaferri
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cesinaro
authors.forename: Roberta
authors.initials: R
authors.lastname: Depenni
authors.forename: Paola
authors.initials: P
authors.lastname: Manni
authors.forename: Fabio
authors.initials: F
authors.lastname: Gelsomino
authors.forename: Francesca
authors.initials: F
authors.lastname: Giusti
authors.forename: Lorella
authors.initials: L
authors.lastname: Garagnani
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D005188:False Negative Reactions; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012737:Sex Factors; D012878:Skin Neoplasms; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf