title: BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival.
abstract: BACKGROUND
  Around 50% of primary melanomas harbour BRAF mutations, but their prognostic impact has not been clear. Recently, a BRAF-V600E mutation-specific antibody has become available for immunohistochemistry. Here, we investigated for the first time the prognostic impact of BRAF-V600E protein expression in primary melanoma.
  
  
  METHODS
  In a patient series of 248 nodular melanomas, BRAF-V600E and total BRAF expression were assessed by immunohistochemistry using tissue microarray sections of paraffin-embedded archival tissue. Mutation status was assessed by real-time PCR in cases with sufficient tumour tissue (n=191).
  
  
  RESULTS
  Positive BRAF-V600E expression was present in 86 (35%) of the cases, and was significantly associated with increased tumour thickness, presence of tumour ulceration and reduced survival. Further, BRAF-V600E expression was an independent prognostic factor by multivariate analysis, whereas BRAF mutation status was not significant. There was 88% concordance between BRAF-V600E expression and mutation status.
  
  
  CONCLUSIONS
  Our findings indicate that BRAF-V600E expression is a novel prognostic marker in primary melanoma.
authors.affiliation: Centre for Cancer Biomarkers (CCBIO), Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.
authors.forename: Emilia
authors.initials: E
authors.lastname: Hugdahl
authors.affiliation: Centre for Cancer Biomarkers (CCBIO), Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.
authors.forename: May Britt
authors.initials: MB
authors.lastname: Kalvenes
authors.affiliation: Centre for Cancer Biomarkers (CCBIO), Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.
authors.forename: Hanne E
authors.initials: HE
authors.lastname: Puntervoll
authors.affiliation: Centre for Cancer Biomarkers (CCBIO), Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.|Department of Dermatology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Rita G
authors.initials: RG
authors.lastname: Ladstein
authors.affiliation: Centre for Cancer Biomarkers (CCBIO), Department of Clinical Medicine, University of Bergen, 5021 Bergen, Norway.|Department of Pathology, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D046888:Tissue Array Analysis; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf