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

Kakavand, Hojabr1,2; Crainic, Oana3,4; Lum, Trina3; O’Toole, Sandra A.1,3,5; Kefford, Richard F.1,2; Thompson, John F.1,2,6; Wilmott, James S.2; Long, Georgina V.1,2; Scolyer, Richard A.1,2,3

doi: 10.1097/PAT.0000000000000077
Anatomical Pathology

Summary: 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 BRAFV600E 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 BRAFV600E 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.

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

Address for correspondence: Mr H. Kakavand, Level 3, Gloucester House, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. E-mail:

Received 8 September, 2013

Revised 15 October, 2013

Accepted 17 October, 2013

© 2014 Royal College of Pathologists of Australasia
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