BRAF~(V600E)基因突变与甲状腺微小乳头状癌中央区淋巴结转移相关性研究
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摘要
目的回顾性分析V-RAF小鼠肉瘤病毒癌基因同源物B1(BRAF)基因突变与甲状腺微小乳头状癌(PTMC)中央区淋巴结转移的相关性。方法应用实时荧光定量PCR基因测序法,检测200例行中央区淋巴结清扫的PTMC患者石蜡包埋组织中BRAF~(V600E)基因突变情况,结合临床病理资料,分析BRAF~(V600E)基因和PTMC中央区淋巴结转移的相关性。结果 PTMC患者BRAF~(V600E)突变的发生率为84.5%(169/200)。单变量和多变量分析均显示BRAF~(V600E)突变与中央区淋巴结转移之间存在相关性(P<0.05)。对于肿瘤直径>5mm且≤10mm的患者,BRAF~(V600E)突变与中央区淋巴结转移相关(P=0.037)。结论 BRAF~(V600E)突变、肿瘤大小有助于预测PTMC患者的中央区淋巴结转移情况,对有BRAF~(V600E)突变且直径>5mm的PTMC宜常规行中央区淋巴结清扫。
Objective To explore the association v-raf murine sarcoma viral oncogene homolog B1(BRAF~(V600E)) gene mutation and central lymph node metastasis in papillary thyroid microcarcinoma(PTMC). Methods Real-time PCR sequencing was used to detect the BRAF~(V600E)gene mutation in 200 paraffin-embedded tissue samples of PTMC with central lymph node dissection. The correlation of BRAF~(V600E)mutation with central lymph node metastasis was analyzed. Results The incidence of BRAF~(V600E)mutation in patients with PTMC was 84.5%(169/200). Univariate and multivariate analyses indicated a correlation between BRAF~(V600E)mutation and central lymph node metastasis(P<0.05). For patients with tumors >5 and ≤10 mm in diameter, BRAF~(V600E)mutation was significantly associated with central lymph node metastasis(P=0.037). Conclusion BRAF~(V600E)gene mutation and the tumor size may be used to predict the central lymph node metastasis in patients with PTMC.
Objective To explore the association v-raf murine sarcoma viral oncogene homolog B1(BRAF~(V600E)) gene mutation and central lymph node metastasis in papillary thyroid microcarcinoma(PTMC). Methods Real-time PCR sequencing was used to detect the BRAF~(V600E)gene mutation in 200 paraffin-embedded tissue samples of PTMC with central lymph node dissection. The correlation of BRAF~(V600E)mutation with central lymph node metastasis was analyzed. Results The incidence of BRAF~(V600E)mutation in patients with PTMC was 84.5%(169/200). Univariate and multivariate analyses indicated a correlation between BRAF~(V600E)mutation and central lymph node metastasis(P<0.05). For patients with tumors >5 and ≤10 mm in diameter, BRAF~(V600E)mutation was significantly associated with central lymph node metastasis(P=0.037). Conclusion BRAF~(V600E)gene mutation and the tumor size may be used to predict the central lymph node metastasis in patients with PTMC.
引文
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[20]Vorasubin N,Nguyen C,Wang M.Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma:A meta-analysis[J].Ear Nose Throat J,2016,95(2):73-77.
[21]Rossi ED,Martini M,Capodimonti S,et al.BRAF(V600E)mutation analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma[J].Cancer Cytopathol,2013,121(6):291-297.DOI:10.1002/cncy.21258.
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[2]Pellegriti G,Frasca F,Regalbuto C,et al.Worldwide increasing incidence of thyroid cancer:update on epidemiology and risk factors[J].JCancer Epidemiol,2013,965212.DOI:10.1155/2013/965212.
[3]Hughes DT,Haymart MR,Miller BS,et al.The most commonly occurring papillary thyroid cancer in the United States is now a microcarcinoma in a patient older than 45 years[J].Thyroid,2011,21(3):231-236.DOI:10.1089/thy.2010.0137.
[4]Qu H,Sun G R,Liu Y,et al.Clinical risk factors for central lymph node metastasis in papillary thyroid carcinoma:a systematic review and meta-analysis[J].Clin Endocrinol(Oxf),2015,83(1):124-132.DOI:10.1111/cen.12583.
[5]Plzák J,Astl J,Psychogios G,et al.Current treatment strategies for papillary thyroid microcarcinoma[J].HNO,2013,61(4):300-305.DOI:10.1007/s00106-013-2679-2.
[6]高明,葛明华,嵇庆海,等.甲状腺微小乳头状癌诊断与治疗中国专家共识(2016版)[J].中国肿瘤临床,2016,43(10):526.DOI:10.3969/j.issn.1000-8179.2016.10.001.
[7]Xing M,Alzahrani AS,Carson KA,et al.Association between BRAFV600E mutation and recurrence of papillary thyroid cancer[J].J Clin Oncol,2015,33(1):42-50.DOI:10.1200/JCO.2014.56.8253.
[8]Fei L,Guangqi C,Chunjun S,et al.BRAFV600E mutation in papillary thyroid microcarcinoma:a meta-analysis[J].Endocrine Related Cancer,2015,22(2):159.DOI:10.1530/ERC-14-0531.
[9]Sun Y,Shi C,Shi T,et al.Correlation between the BRAF(v600E)gene mutation and factors influencing the prognosis of papillary thyroid microcarcinoma[J].Int J Clin Exp Med,2015,8(12):22525-22528.
[10]Bal C,Ballal S.Is there any true association between BRAF V600E mutation and recurrence,particularly in low-risk,papillary thyroid cancer[J].J Clin Oncol,2015,33(22):2481.DOI:10.1200/JCO.2014.60.0999.
[11]Chen Y,Sadow PM,Suh H,et al.BRAF(V600E)is correlated with recurrence of papillary thyroid microcarcinoma:a systematic review,multi-institutional primary data analysis,and Metaanalysis[J].Thyroid,2016,26(2):248-255.DOI:10.1089/thy.2015.0391.
[12]Xing M,Alzahrani AS,Carson KA,et al.Association between BRAFV600E mutation and mortality in patients with papillary thyroid cancer[J].JAMA,2013,309(14):1493-1501.DOI:10.1001/jama.2013.3190.
[13]Zhao Q,Ming J,Liu C,et al.Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma[J].Ann Surg Oncol,2013,20(3):746-752.DOI:10.1245/s10434-012-2654-2.
[14]Shiva M,Haling JR,Sudhamsu J,et al.Abstract 2346:A B-RAF-MEK complex reveals a kinase-independent role for BRAF in MAPKpathway suppression[J].Cancer Research,2013,73(8 Supplement):2346-2346.DOI:10.1158/1538-7445.AM2013-2346.
[15]张玉洁,刘宝国,赵治艳,等.甲状腺乳头状癌中BRAF基因突变与中央区淋巴结转移的关系及临床意义[J].北京大学学报(医学版),2016,48(3):502-506.DOI:10.3969/j.issn.1671-167X.2016.03.022.
[16]Shi CL,Sun Y,Ding C,et al.Correlation between the BRAF V600Emutation status and the clinicopathologic features of papillary thyroid carcinoma[J].Genet Mol Res,2015,14(3):7377-7385.DOI:10.4238/2015.July.3.13.
[17]Fraser S,Go C,Aniss A,et al.BRAF(V600E)mutation is associated with decreased disease-free survival in papillary thyroid cance r[J].World J Surg,2016,40(7):1618-1624.DOI:10.1007/s00268-016-3534-x.
[18]Zheng X,Wei S,Han Y,et al.Papillary microcarcinoma of the thyroid:clinical characteristics and BRAF(V600E)mutational status of 977 cases[J].Ann Surg Oncol,2013,20(7):2266-2273.DOI:10.1245/s10434-012-2851-z.
[19]Wang M,Wu WD,Chen GM,et al.Could tumor size be a predictor for papillary thyroid microcarcinoma:a retrospective Cohort study[J].Asian Pac J Cancer Prev,2015,16(18):8625-8628.DOI:10.7314/APJCP.2015.16.18.8625.
[20]Vorasubin N,Nguyen C,Wang M.Risk factors for cervical lymph node metastasis in papillary thyroid microcarcinoma:A meta-analysis[J].Ear Nose Throat J,2016,95(2):73-77.
[21]Rossi ED,Martini M,Capodimonti S,et al.BRAF(V600E)mutation analysis on liquid-based cytology-processed aspiration biopsies predicts bilaterality and lymph node involvement in papillary thyroid microcarcinoma[J].Cancer Cytopathol,2013,121(6):291-297.DOI:10.1002/cncy.21258.
[22]Lee WS,Palmer BJ,Garcia A,et al.BRAF mutation in papillary thyroid cancer:A cost-utility analysis of preoperative testing[J].Surgery,2014,156(6):1569-1578.DOI:10.1016/j.surg.2014.08.051.
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