title: Concordant BRAFV600E mutation status in primary melanomas and associated naevi: implications for mutation testing of primary melanomas.
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.
authors.affiliation: 1The University of Sydney, Sydney 2Melanoma Institute Australia, North Sydney 3Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia 4Canterbury Health Laboratories, Christchurch, New Zealand 5Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst 6Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Hojabr
authors.initials: H
authors.lastname: Kakavand
authors.forename: Oana
authors.initials: O
authors.lastname: Crainic
authors.forename: Trina
authors.initials: T
authors.lastname: Lum
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: James S
authors.initials: JS
authors.lastname: Wilmott
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf