1] Melanoma Institute Australia, Sydney, New South Wales, Australia [2] Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead, New South Wales, Australia [3] Department of Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, Australia [4] Discipline of Medicine, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
1] Melanoma Institute Australia, Sydney, New South Wales, Australia [2] Discipline of Surgery, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Br J Cancer. 2014 Jul 15;111(2):292-9. doi: 10.1038/bjc.2014.287. Epub 2014 Jun 10.
BACKGROUND: The prognostic significance of BRAF and NRAS mutations in metastatic melanoma patients remains uncertain, with several studies reporting conflicting results, often biased by the inclusion of patients treated with BRAF and MEK (MAPK) inhibitors. We therefore interrogated a historical cohort of patients free of the confounding influence of MAPK inhibitor therapy. METHODS: Patients with available archival tissue first diagnosed with metastatic melanoma between 2002 and 2006 were analysed. Mutational analysis was performed using the OncoCarta Panel. Patient characteristics, treatment outcome and survival were correlated with BRAF/NRAS mutation status. RESULTS: In 193 patients, 92 (48%) melanomas were BRAF-mutant, 39 (20%) were NRAS-mutant and 62 (32%) were wild-type for BRAF/NRAS mutations (wt). There was no difference in response to chemotherapy based on mutation status (35-37%). The distant disease-free interval (DDFI) was significantly shorter in patients with wt melanoma (27.9 months vs 35.1 for BRAF and 49.1 for NRAS) although this was not significant in multivariate analysis. Survival from stage IV melanoma diagnosis was not significantly different based on mutation status. The DDFI was significantly shorter in patients with BRAF(V600K/R) versus BRAF(V600E) melanoma in univariate and multivariate analyses. CONCLUSIONS: BRAF and NRAS mutation status does not influence survival in metastatic melanoma.
背景：BRAF 和 NRAS 突变在转移性黑色素瘤患者中的预后意义仍不确定，多项研究报告的结果相互矛盾，这往往受到包括接受 BRAF 和 MEK（MAPK）抑制剂治疗的患者的影响。因此，我们调查了一组没有受到 MAPK 抑制剂治疗影响的历史患者队列。
方法：分析了 2002 年至 2006 年间首次诊断为转移性黑色素瘤且有可用存档组织的患者。使用 OncoCarta 试剂盒进行突变分析。患者特征、治疗结果和生存情况与 BRAF/NRAS 突变状态相关。
结果：在 193 名患者中，92 名（48%）黑色素瘤为 BRAF 突变型，39 名（20%）为 NRAS 突变型，62 名（32%）为 BRAF/NRAS 突变野生型（wt）。根据突变状态，化疗的反应没有差异（35-37%）。wt 黑色素瘤患者的远处无病间隔（DDFI）明显较短（27.9 个月 vs BRAF 的 35.1 个月和 NRAS 的 49.1 个月），尽管这在多变量分析中并不显著。根据突变状态，IV 期黑色素瘤诊断后的生存时间没有显著差异。单变量和多变量分析均显示，BRAF(V600K/R) 与 BRAF(V600E) 黑色素瘤患者的 DDFI 明显较短。
结论：BRAF 和 NRAS 突变状态并不影响转移性黑色素瘤的生存。
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