Melanoma Institute Australia, Disciplines of Medicine, Surgery, Pathology, and Westmead Institute for Cancer Research, Westmead Millennium Institute, The University of Sydney, Sydney, New South Wales, Australia.
Clin Cancer Res. 2012 Jun 15;18(12):3242-9. doi: 10.1158/1078-0432.CCR-12-0052. Epub 2012 Apr 24.
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.
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.
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).
Different genotypes exist within BRAF-mutant metastatic melanoma, representing biologically and clinically discrete subtypes, suggesting distinct etiology and behavior.
某些临床病理特征与黑色素瘤中的 BRAF 突变状态相关，包括年龄较轻和原发性亚型。本研究旨在通过年龄十年确定 BRAF 突变状态，以及 BRAF 突变基因型是否与转移性黑色素瘤患者的临床病理特征和结局相关。
前瞻性地收集了澳大利亚转移性黑色素瘤患者的队列（N=308）。将临床病理变量与 BRAF 突变状态、基因型和生存相关联。
46%的患者存在 BRAF 突变；73%为 V600E、19%为 V600K、8%为其他基因型。BRAF 突变流行率与年龄十年呈负相关（P<0.001）。所有<30 岁的患者和仅 25%≥70 岁的患者均存在 BRAF 突变黑色素瘤。在 BRAF 突变黑色素瘤中，非 V600E 基因型（包括 V600K）的频率随着年龄的增加而增加。<50 岁的患者中<20%为非 V600E 基因型，≥70 岁的患者中>40%为非 V600E 基因型。累积太阳诱导损伤程度与 V600K 相关性更高，但与 V600E 黑色素瘤无关（P=0.002）。与 V600E 黑色素瘤相比，V600K 黑色素瘤患者从原发性黑色素瘤诊断到首次远处转移的无病间隔更短（17.4 与 39.2 个月，P=0.048），此后的生存无差异。在接受转移性黑色素瘤诊断时进行 BRAF 检测的患者中，BRAF 突变黑色素瘤患者接受抑制剂治疗的一年生存率显著高于未接受抑制剂治疗的患者（83%与 29%，P<0.001），也高于 BRAF 野生型黑色素瘤患者（37%，P<0.001）。
BRAF 突变型转移性黑色素瘤存在不同的基因型，代表生物学和临床上不同的亚型，提示存在不同的病因和行为。
