Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2012 Aug 15;118(16):4014-23. doi: 10.1002/cncr.26724. Epub 2011 Dec 16.
There is a need for improved prognostic markers in melanoma. In this study, the authors tested the prognostic significance and clinicopathologic correlations of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) and neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutations in patients with metastatic melanoma.
Clinical and pathologic data were collected retrospectively on melanoma patients who were clinically tested for BRAF (exon 15) and NRAS (exons 1 and 2) mutations at The University of Texas M. D. Anderson Cancer Center. Analyses were performed to identify significant associations of mutations with tumor and patient characteristics and with survival from the diagnosis of stage IV disease.
The genotypes of the full cohort (n = 677) were 47% BRAF mutation, 20% NRAS mutation, and 32% wild-type for BRAF and NRAS ("WT"). Tumor mutation status was associated (P = .008) with the risk of central nervous system involvement at the diagnosis of stage IV disease, with a higher prevalence observed in BRAF-mutant (24%) and NRAS-mutant (23%) patients than in WT patients (12%). Among patients with nonuveal melanoma who underwent mutation testing within 6 months of stage IV diagnosis (n = 313), patients with NRAS mutations had a median survival of 8.2 months from stage IV diagnosis, which was shorter than the median survival of WT patients (15.1 months; P = .004). Multivariate analysis of this population incorporating age, sex, metastases (M1) category, serum lactate dehydrogenase level, and mutation status confirmed that NRAS mutations are associated independently with decreased overall survival (vs WT; P = .005; hazard ratio, 2.05).
Patients with BRAF or NRAS mutations were more likely than WT patients to have central nervous system involvement at the time they were diagnosed with distant metastatic disease. NRAS mutation status was identified as an independent predictor of shorter survival after a diagnosis of stage IV melanoma.
黑色素瘤需要更好的预后标志物。在这项研究中，作者检测了转移性黑色素瘤患者中 v-raf 鼠肉瘤病毒癌基因同源物 B1（BRAF）和神经母细胞瘤 RAS 病毒（v-ras）癌基因同源物（NRAS）突变的预后意义和临床病理相关性。
在德克萨斯大学 MD 安德森癌症中心对黑色素瘤患者进行 BRAF（外显子 15）和 NRAS（外显子 1 和 2）突变的临床检测，回顾性收集临床和病理数据。进行分析以确定突变与肿瘤和患者特征以及从 IV 期疾病诊断开始的生存之间的显著关联。
全队列（n=677）的基因型为 47% BRAF 突变、20% NRAS 突变和 32% BRAF 和 NRAS“WT”野生型。肿瘤突变状态与 IV 期疾病诊断时中枢神经系统受累的风险相关（P=0.008），BRAF 突变（24%）和 NRAS 突变（23%）患者比 WT 患者（12%）更常见。在 6 个月内接受 IV 期诊断后突变检测的非脉络膜黑色素瘤患者（n=313）中，NRAS 突变患者从 IV 期诊断开始的中位生存期为 8.2 个月，短于 WT 患者（15.1 个月；P=0.004）。对该人群进行的多变量分析纳入了年龄、性别、转移（M1）类别、血清乳酸脱氢酶水平和突变状态，证实 NRAS 突变与总生存期缩短独立相关（与 WT 相比；P=0.005；风险比，2.05）。
与 WT 患者相比，BRAF 或 NRAS 突变患者在诊断为远处转移性疾病时更有可能出现中枢神经系统受累。NRAS 突变状态被确定为 IV 期黑色素瘤诊断后生存时间较短的独立预测因子。
