Data from Distinguishing Clinicopathologic Features of Patients with V600E and V600K <i>BRAF</i>-Mutant Metastatic Melanoma

Abstract

<div>Abstract<p><b>Purpose:</b> Certain clinicopathologic features correlate with <i>BRAF</i> mutation status in melanoma including younger age and primary subtype. This study sought to determine the <i>BRAF</i> mutation status by age-decade and whether <i>BRAF</i>-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma.</p><p><b>Methods:</b> A prospectively assembled cohort of Australian patients were followed from diagnosis of metastatic melanoma (N = 308). Clinicopathologic variables were correlated with <i>BRAF</i> mutational status, genotype, and survival.</p><p><b>Results:</b> Forty-six percent of patients had a <i>BRAF</i> mutation; 73% V600E, 19% V600K, and 8% other genotypes. An inverse relationship existed between <i>BRAF</i> mutation prevalence and age-decade (<i>P</i> < 0.001). All patients <30 years and only 25% ≥70 years had <i>BRAF</i>-mutant melanoma. Amongst <i>BRAF</i>-mutant melanoma, the frequency of non-V600E genotypes (including V600K) increased with increasing age. Non-V600E genotypes comprised <20% in patients <50 years and >40% in those ≥70 years. A higher degree of cumulative sun-induced damage correlated with V600K but not V600E melanoma (<i>P</i> = 0.002). The disease-free interval from diagnosis of primary melanoma to first distant metastasis was shorter for patients with V600K compared with V600E melanoma (17.4 vs. 39.2 months, <i>P</i> = 0.048), with no difference in survival thereafter. In patients <i>BRAF</i> tested at diagnosis of metastatic melanoma, one year survival from diagnosis of metastasis was significantly longer for patients with <i>BRAF</i>-mutant melanoma treated with an inhibitor (83%), than those not treated with an inhibitor (29%, <i>P</i> < 0.001), or patients with <i>BRAF</i> wild-type melanoma (37%, <i>P</i> < 0.001).</p><p><b>Conclusion:</b> Different genotypes exist within <i>BRAF</i>-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior. <i>Clin Cancer Res; 18(12); 3242–9. ©2012 AACR</i>.</p></div>