甲状腺乳头状癌BRAF V600E、TERT和RET分子检测及与临床病理特征的关系  

Correlation between clinicopathological characteristics and BRAF V600E,TERT,RET gene in papillary thyroid carcinoma

作　　者：尚轶钒 黄思夏 王佳鹤 王玉姣 陈伶俐 张慧娟 李烨[1] 王蕾[1] 吕新全[1] SHANG Yi-fan;HUANG Si-xia;WANG Jia-he;WANG Yu-jiao;CHEN Ling-li;ZHANG Hui-juan;LI Ye;WANG Lei;LÜXin-quan(Department of Pathology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院病理科,郑州450052

出　　处：《临床与实验病理学杂志》2023年第6期661-667,共7页Chinese Journal of Clinical and Experimental Pathology

基　　金：河南省高等学校重点科研项目(22A310023)。

摘　　要：目的探讨甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中三种驱动基因BRAF V600E、TERT和RET与临床病理特征的关系。方法收集4678例PTC,2637例患者行BRAF V600E和TERT启动子检测(C250T和C228T位点),另2041例患者行BRAF V600E和RET检测,并分析以上3种基因与临床病理特征的关系。结果PTC中BRAF V600E、TERT及RET基因阳性检出率分别为88.9%(4161/4678)、0.5%(12/2637)、3.7%(75/2041)。BRAF V600E突变仅与被膜侵犯及桥本甲状腺炎伴随相关(P<0.05);TERT启动子突变与患者年龄、肿瘤最大径、肿瘤数量、淋巴结转移、TNM分期均有关(P<0.05);RET基因融合与患者性别、肿瘤最大径、淋巴结转移、桥本甲状腺炎伴随有关(P<0.05)。双基因改变患者合计12例,包括1例BRAF V600E突变伴CCDC6-RET(Exon1-Exon12)基因重排变异,1例BRAF V600E突变伴NCOA4-RET(Exon6-Exon12/partial Exon7-Exon12)基因重排变异,10例BRAF V600E伴TERT启动子双突变。BRAF V600E伴TERT双突变在>55岁、较大肿瘤、多癌灶、有淋巴结转移或晚期患者中更易发生(P<0.05)。结论BRAF V600E在PTC中突变率极高,提示可作为PTC诊断的重要分子学依据;TERT及RET基因改变可反映肿瘤侵袭性生物学行为并提示预后不佳,两者均可伴有BRAF V600E突变,且BRAF V600E和TERT双突变提示更差的临床预后,因此联合多基因检测可更全面评估患者预后风险,为疾病预后分层及临床个性化治疗策略提供分子基础。Purpose To explore the correlation between three driver genes(BRAF V600E,TERT,RET)and clinicopathological characteristics of papillary thyroid carcinoma(PTC).Method A total of 4678 patients with PTC were collected.BRAF V600E and TERT promoter(C250T and C228T sites)were detected in 2637 patients,BRAF V600E and RET were detected in the rest.The relationship between the above three genes and clinicopathological features was analyzed.Results The positive rates of BRAF V600E,TERT and RET were 88.9%(4161/4678),0.5%(12/2637)and 3.7%(75/2041)in PTC patients,respectively.BRAF V600E mutations were only associated with capsular invasion and Hashimoto’s thyroiditis(P<0.05).TERT promoter mutations were associated with age,tumor size,tumor number,lymph node metastasis and TNM stage(P<0.05).RET fusions were associated with gender,tumor size,lymph node metastasis,and Hashimoto’s thyroiditis(P<0.05).There were 12 patients showed double gene alterations,including 1 case of BRAF V600E mutation with CCDC6-RET(Exon1-Exon12)gene rearrangement,1 case of BRAF V600E mutation with NCOA4-RET(Exon6-Exon12/partial Exon7-Exon12)gene rearrangement and 10 comutations of BRAF V600E and TERT promoter.BRAF V600E and TERT comutations were most likely to occur in patients who were over 55 years old,with larger size of tumors,multiple foci,lymph node metastases,or advanced stages(P<0.05).Conclusion The mutation rate of BRAF V600E in PTC is extremely high,suggesting that BRAF V600E can be used as an important molecular basis for the diagnosis of PTC.TERT and RET gene changes can reflect the invasive biological behavior of tumors and indicate poor prognosis,both of which may be accompanied by BRAF V600E gene mutations,and the comutations of BRAF V600E and TERT genes suggest poor prognosis.Therefore,multi-gene testing can be used to assess the prognosis risk of patients more comprehensively,provide the molecular basis for stratification of disease prognosis and clinical personalized treatment strategy.

关 键 词：甲状腺乳头状癌 BRAF V600E TERT RET 多基因改变 

分 类 号：R736.1[医药卫生—肿瘤]