Concordant BRAFV600E mutation status in primary melanomas and associated naevi: implications for mutation testing of primary melanomas

Pathology. 2014 Apr;46(3):193-8. doi: 10.1097/PAT.0000000000000077.

Abstract

There is concern that BRAF mutant naevus cells admixed with melanoma cells could cause false positive mutation tests in BRAF wild-type melanomas. We sought to assess the frequency of BRAF(V600E) mutations in primary melanomas arising with/without associated naevi and determine BRAF(V600E) concordance between melanomas and associated naevi. Formalin fixed, paraffin embedded (FFPE) tissue from 57 patients with primary melanomas with/without associated naevi was immunohistochemically stained to detect BRAF(V600E) mutation. In a subset of patients (n = 29), molecular mutation testing was also carried out using a panel of 238 known genetic variants. Of the primary melanomas with an associated naevus (n = 29), 55% were BRAF(V600E) mutant with 100% concordance between the melanoma and associated naevus. In contrast, only 21% of the primary melanomas unassociated with naevi were BRAF(V600E) mutant (p = 0.009).Our results suggest that melanomas with associated naevi have a higher frequency of BRAF(V600E) mutations than melanomas unassociated with naevi. Furthermore, melanomas and their associated naevi were concordant in BRAF(V600E) status, which suggests that false positive mutation tests occurring as a consequence of admixed BRAF mutant naevus cells in BRAF wild-type primary melanomas are unlikely to be a problem in clinical practice. The findings have important implications for adjuvant clinical trials of targeted therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma / diagnosis
  • Melanoma / genetics*
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

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