BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer With Highest Recurrence
BRAF V600E and TERT Promoter Mutations Cooperatively Identify the Most Aggressive Papillary Thyroid Cancer With Highest Recurrence
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DOI：
10.1200/jco.2014.55.5094
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发表时间：
2014-09-01
影响因子：
45.3
通讯作者：
Bishop, Justin
中科院分区：
文献类型：
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作者：
Xing, Mingzhao;Liu, Rengyun;Bishop, Justin
目的探讨BRAF V600E突变和新近发现的TERT启动子突变chr5：1,295,228C>对预后的影响；方法对507例患者(女性365例，男性142例)的BRAF和TERT C228T突变与甲状腺乳头状癌(PTC)临床病理结果的关系进行了回顾性研究。肿瘤复发率分别为25.8%(50/194；77.60/1,000人年；95%CI，58.81~102.38)和9.6%(30/313，22.88/1,000人年；95%CI，16.00~32.72)和47.5%(29/61,108.55/1,000人年；TERT基因突变阳性与阴性患者的95%可信区间分别为75.43~156.20和11.4%(51/446；每千人年复发率30.21；95%可信区间22.96~39.74)。复发率分别为68.6%(24/35；每千人年复发率211.76；95%CI，141.94~315.94)和8.7%(25/287，每千人年复发率21.60；95%CI，14.59~31.97)。BRAF V600E或TERT C228T单独存在时，患者无病生存曲线呈中度下降趋势，但两种突变同时存在时，患者生存曲线急剧下降。结论BRAF V600E和TERT C228T突变共同构成了一个新的遗传背景，决定了PTC的临床病理转归最差，具有独特的预后和治疗意义。(C)美国临床肿瘤学会2014年
PurposeTo investigate the prognostic value of the BRAF V600E mutation and the recently identified TERT promoter mutation chr5:1,295,228C > T (C228T), individually and in their coexistence, in papillary thyroid cancer (PTC).Patients and MethodsWe performed a retrospective study of the relationship of BRAF and TERT C228T mutations with clinicopathologic outcomes of PTC in 507 patients (365 women and 142 men) age 45.9 +/- 14.0 years (mean +/- SD) with a median follow-up of 24 months (interquartile range, 8 to 78 months).Results Coexisting BRAF V600E and TERT C228T mutations were more commonly associated with high-risk clinicopathologic characteristics of PTC than they were individually. Tumor recurrence rates were 25.8% (50 of 194; 77.60 recurrences per 1,000 person-years; 95% CI, 58.81 to 102.38) versus 9.6% (30 of 313; 22.88 recurrences per 1,000 person-years; 95% CI, 16.00 to 32.72) in BRAF mutation-positive versus -negative patients (hazard ratio [HR], 3.22; 95% CI, 2.05 to 5.07) and 47.5% (29 of 61; 108.55 recurrences per 1,000 person-years; 95% CI, 75.43 to 156.20) versus 11.4% (51 of 446; 30.21 recurrences per 1,000 person-years; 95% CI, 22.96 to 39.74) in TERT mutation-positive versus - negative patients (HR, 3.46; 95% CI, 2.19 to 5.45). Recurrence rates were 68.6% (24 of 35; 211.76 recurrences per 1,000 person-years; 95% CI, 141.94 to 315.94) versus 8.7% (25 of 287; 21.60 recurrences per 1,000 person-years; 95% CI, 14.59 to 31.97) in patients harboring both mutations versus patients harboring neither mutation (HR, 8.51; 95% CI, 4.84 to 14.97), which remained significant after clinicopathologic cofactor adjustments. Disease-free patient survival curves displayed a moderate decline with BRAF V600E or TERT C228T alone but a sharp decline with two coexisting mutations.ConclusionCoexisting BRAF V600E and TERT C228T mutations form a novel genetic background that defines PTC with the worst clinicopathologic outcomes, providing unique prognostic and therapeutic implications. (C) 2014 by American Society of Clinical Oncology