基于年龄分层BRAF-V600^E基因突变对甲状腺乳头状癌的临床意义  

Clinical implication of age-stratified BRAF-V600E mutation in papillary thyroid carcinoma

作　　者：甘枭雄 蔡文松[1] 沈飞[1] 冯键华 徐波[1] Gan Xiaoxiong;Cai Wensong;Shen Fei;Feng Jianhua;Xu Bo(Department of Thyroid Surgery,Guangzhou First People’s Hospital,Guangzhou Medical University,Guangzhou 510000,China)

机构地区：[1]广州医科大学附属广州市第一人民医院甲状腺外科,510000

出　　处：《中华生物医学工程杂志》2020年第2期128-136,共9页Chinese Journal of Biomedical Engineering

基　　金：广州市卫生健康科技项目(20171A011243)。

摘　　要：目的探讨BRAF-V600^E突变对甲状腺乳头状癌(PTC)的临床病理意义。方法回顾性分析2016年1月至2019年3月本院甲状腺外科诊治的331例术后病理诊断为PTC患者的临床资料。利用基于实时荧光定量聚合酶链式反应(RT-PCR)技术的扩增阻滞突变系统(ARMS)检测BRAF-V600^E突变。根据8版美国癌症联合委员会(AJCC)年龄风险分层,以55岁为年龄切点值,将患者分为<55岁组和≥55岁组。运用χ^2检验或Fisher精确检验分析BRAF-V600^E突变状态与临床病理特征之间的相关性,采用Cox多元回归分析向前逐步回归法分析两组患者肿瘤复发风险,运用Kaplan-Meier检验分析两组患者肿瘤无复发生存(RFS)。结果共236例(71.3%)发生BRAF-V600^E突变。在<55岁组共210例PTC患者,145(69.0%)例PTC为BRAF-V600^E变异型。BRAF-V600^E基因的突变与桥本氏甲状腺炎、组织学亚型、淋巴结转移、碘放射治疗(RAI)剂量、中或高复发风险、T分期有关(均P<0.05);在≥55岁组共121例PTC患者,91例(75.2%)为BRAF-V600^E变异型,BRAF-V600^E基因突变与肿瘤大小、桥本氏甲状腺炎、组织学亚型、RAI剂量、中或高复发风险、T分期、N分期、AJCC分期(Ⅲ/Ⅳ)有关(均P<0.05)。BRAF-V600^E基因在<55岁组不能独立预测肿瘤复发,但是在≥55岁组,BRAF-V600^E基因、男性、多灶癌、N分期、M分期都纳入COX回归方程中,是PTC复发的相关因素(均P<0.05),≥55岁组对比<55岁组PTC患者有明显更高的复发风险(P=0.032)。≥55岁组中位RFS为43.4个月,5年肿瘤无复发生存率为62.1%;<55岁组为78.7个月,5年肿瘤无复发生存率为88.2%。<55岁组中,BRAF-V600^E变异组与BRAF-V600^E野生组患者的肿瘤无复发生存曲线差异无统计学意义(P=0.334);BRAF-V600^E变异组与BRAF-V600^E野生组患者的RFS生存曲线差异有统计学意义(P<0.05),变异组患者中位RFS为13个月,5年肿瘤无复发生存率为35.5%;野生组患者中位RFS为101.3个月,5年肿瘤无复发生存率为Objective To determine the clinicopathological implication of BRAF-V600^E mutation in thyroid papillary carcinoma(PTC).Methods The clinical data of 331 patients diagnosed with PTC between January 2016 and March 2019 in Department of Thyroid Surgery,Guangzhou First People’s Hospital,were analyzed retrospectively.Detection for the BRAF-V600^E mutation was completed by amplification refractory mutation system(ARMS)using quantitative real-time PCR(RT-PCR).According to the 8th edition of the American Joint Committee on Cancer(AJCC)age risk stratification,the patients were divided into the<55-year-old group and the≥55-year-old group with age cut-off value of 55 years.The relationship between BRAF-V600^E mutation and clinicopathological characteristics was analyzed byχ^2 test or Fisher's exact test.Multivariate Cox regression analysis was used to analyze the risk of tumor recurrence in two groups of patients.Recurrence-free survival rate(RFS)was analyzed using the Kaplan-Meier method.Results The BRAF-V600^E mutation was detected in 236 of 331(71.3%)PTC patients.The<55-year-old group comprised 210 PTC patients,among which,BRAF-V600^E mutation was detected in 145(69.0%),and was associated with Hashimoto's thyroiditis,histological subtype,lymph node metastasis,Radioactive iodine(RAI)dose,moderate/high recurrence risk,and T staging(all P<0.05).The≥55-year-old group comprised 121 PTC patients,among which,BRAF-V600^E mutation was detected in 91(75.2%),and was associated with tumor size,Hashimoto's thyroiditis,histological subtype,RAI dose,moderate/high recurrence risk,T and N stagings,and AJCC stagesⅢ/Ⅳ(all P<0.05).BRAF-V600^E mutation was not an independent predictor of tumorrecurrencein the<55-year-old group.However,in the≥55-year-old group,BRAF-V600^E mutation,male,multiple lesions,N and M stagings were part of Cox regression equation,and were all related to the recurrence of PTC(all P<0.05).Themedian RFS and 5-yeartumor-free survival rate was 43.4 months and 62.1%in the≥55-year-old group,compared with 78.7

关 键 词：甲状腺肿瘤 乳头状瘤 BRAF基因 突变 年龄分布 预后 复发 

分 类 号：R736.1[医药卫生—肿瘤]