TY - JOUR
T1 - Concordant BRAFV600E mutation status in primary melanomas and associated naevi
T2 - implications for mutation testing of primary melanomas
AU - Kakavand, Hojabr
AU - Crainic, Oana
AU - Lum, Trina
AU - O'Toole, Sandra A.
AU - Kefford, Richard F.
AU - Thompson, John F.
AU - Wilmott, James S.
AU - Long, Georgina V.
AU - Scolyer, Richard A.
PY - 2014/4
Y1 - 2014/4
N2 - 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 BRAFV600E mutations in primary melanomas arising with/without associated naevi and determine BRAFV600E 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 BRAFV600E mutant (p=0.009). Our results suggest that melanomas with associated naevi have a higher frequency of BRAFV600E mutations than melanomas unassociated with naevi. Furthermore, melanomas and their associated naevi were concordant in BRAFV600E 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.
AB - 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 BRAFV600E mutations in primary melanomas arising with/without associated naevi and determine BRAFV600E 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 BRAFV600E mutant (p=0.009). Our results suggest that melanomas with associated naevi have a higher frequency of BRAFV600E mutations than melanomas unassociated with naevi. Furthermore, melanomas and their associated naevi were concordant in BRAFV600E 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.
UR - http://www.scopus.com/inward/record.url?scp=84902127746&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/nhmrc/633004
U2 - 10.1097/PAT.0000000000000077
DO - 10.1097/PAT.0000000000000077
M3 - Article
VL - 46
SP - 193
EP - 198
JO - Pathology
JF - Pathology
SN - 1465-3931
IS - 3
ER -