BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features and reduced survival

Br J Cancer. 2016 Mar 29;114(7):801-8. doi: 10.1038/bjc.2016.44. Epub 2016 Feb 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Melanoma / genetics
  • Melanoma / mortality*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins B-raf / metabolism
  • Real-Time Polymerase Chain Reaction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / mortality*
  • Skin Neoplasms / pathology
  • Survival Rate
  • Tissue Array Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf