Distinguishing Clinicopathologic Features of Patients with V600E and V600K BRAF-Mutant Metastatic Melanoma

Clinical Cancer Research - Tập 18 Số 12 - Trang 3242-3249 - 2012
Alexander M. Menzies1, Lauren E. Haydu1, Lydia Visintin1, Matteo S. Carlino1, Julie R. Howle1, John F. Thompson1, Richard Kefford1, Richard A. Scolyer1, Georgina V. Long1
1Authors' Affiliations: 1Melanoma Institute Australia; Disciplines of 2Medicine, 3Surgery, 4Pathology, and 5Westmead Institute for Cancer Research, Westmead Millennium Institute, The University of Sydney; 6Westmead Hospital, 7Royal Prince Alfred Hospital, and 8Mater Hospital, Sydney, New South Wales, Australia

Tóm tắt

Abstract Purpose: Certain clinicopathologic features correlate with BRAF mutation status in melanoma including younger age and primary subtype. This study sought to determine the BRAF mutation status by age-decade and whether BRAF-mutant genotypes correlated with clinicopathologic features and outcome in patients with metastatic melanoma. Methods: A prospectively assembled cohort of Australian patients were followed from diagnosis of metastatic melanoma (N = 308). Clinicopathologic variables were correlated with BRAF mutational status, genotype, and survival. Results: Forty-six percent of patients had a BRAF mutation; 73% V600E, 19% V600K, and 8% other genotypes. An inverse relationship existed between BRAF mutation prevalence and age-decade (P < 0.001). All patients <30 years and only 25% ≥70 years had BRAF-mutant melanoma. Amongst BRAF-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 (P = 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, P = 0.048), with no difference in survival thereafter. In patients BRAF tested at diagnosis of metastatic melanoma, one year survival from diagnosis of metastasis was significantly longer for patients with BRAF-mutant melanoma treated with an inhibitor (83%), than those not treated with an inhibitor (29%, P < 0.001), or patients with BRAF wild-type melanoma (37%, P < 0.001). Conclusion: Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior. Clin Cancer Res; 18(12); 3242–9. ©2012 AACR.

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Clinical Cancer Research

Tập 18 Số 12

3242-3249

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