The role of BRAF mutations in primary melanoma growth rate and survival. (13th June 2015)

• Record Type: Journal Article
• Authors: Mar, V.J.; Liu, W.; Devitt, B.; Wong, S.Q.; Dobrovic, A.; McArthur, G.A.; Wolfe, R.; Kelly, J.W.
• Is Part Of: British journal of dermatology. Volume 173:Number 1(2015:Jul.)
• Page Start: 76
• Page End: 82
• Publication Date: 2015-06-13
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.13756
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" id="bjd13756-abs-0001"> <title>Summary</title> <sec id="bjd13756-sec-0001" sec-type="section"> <title>Background</title> <p>The clinical behaviour and prognosis of primary melanomas harbouring <italic>BRAF</italic> mutations is not fully understood.</p> </sec> <sec id="bjd13756-sec-0002" sec-type="section"> <title>Objectives</title> <p>To investigate the effect of mutation status on primary melanoma growth rate and melanoma‐specific survival (MSS).</p> </sec> <sec id="bjd13756-sec-0003" sec-type="section"> <title>Methods</title> <p>A prospective cohort of 196 patients with stage I–III primary cutaneous melanoma were followed for a median of 92 months, pre‐dating the institution of <italic>BRAF</italic> inhibitor therapy. Clinicopathological variables were correlated with mutation status and hazard ratios (HRs) estimated for MSS.</p> </sec> <sec id="bjd13756-sec-0004" sec-type="section"> <title>Results</title> <p>Of 196 tumours, 77 (39·2%) were <italic>BRAF</italic> V600E, 10 (5·1%) <italic>BRAF</italic> V600K and 33 (16·8%) were <italic>NRAS</italic> mutant. <italic>BRAF</italic> V600E mutant melanomas were associated with favourable clinical characteristics and tended to be slower growing compared with <italic>BRAF</italic> V600K, <italic>NRAS</italic> mutant or <italic>BRAF/NRAS</italic> wild‐type tumours (0·12 mm per month, 0·61 mm per month, 0·36 mm per month and 0·23 mm per month, respectively; <italic>P </italic>=<italic> </italic>0·05). There were 39 melanoma deaths, and <italic>BRAF</italic> mutant melanomas were associated with poorer MSS in stage I–III disease [HR 2·60, 95% confidence interval (CI) 1·20–5·63; <italic>P </italic>=<italic> </italic>0·02] and stage I–II disease (HR 3·39, 95% CI 1·12–10·22; <italic>P </italic>=<italic> </italic>0·03) after adjusting for other prognostic variables. Considered separately, <italic>BRAF</italic> V600E mutant melanomas were strongly associated with MSS independently of thickness and nodal status (HR 3·89, 95% CI 1·67–9·09; <italic>P </italic><<italic> </italic>0·01) but <italic>BRAF</italic> V600K mutant tumours were not (HR 1·19, 95% CI 0·36–3·92; <italic>P </italic>=<italic> </italic>0·77).</p> </sec> <sec id="bjd13756-sec-0005" sec-type="section"> <title>Conclusions</title> <p>The presence of a <italic>BRAF</italic> mutation does not necessarily 'drive' more rapid tumour growth but is associated with poorer MSS in patients with early‐stage disease.</p> </sec> </abstract>