山东大学耳鼻喉眼学报 ›› 2020, Vol. 34 ›› Issue (3): 75-80.doi: 10.6040/j.issn.1673-3770.1.2020.022

• 临床研究 • 上一篇    

BRAFV600E突变比值在合并桥本甲状腺炎甲状腺乳头状癌中的初步研究

倪烨钦1,吴凡1,荀延萍2,赵盼3,张仕蓉2,周天晗1,孙思涵4,陆凯宁4,罗定存5   

  1. 1. 浙江中医药大学第四临床医学院, 浙江 杭州 310006;
    2. 浙江大学医学院附属杭州市第一人民医院 转化医学研究中心, 浙江 杭州 310006;
    3. 浙江大学医学院附属杭州市第一人民医院 病理科, 浙江 杭州 310006;
    4. 南京医科大学, 江苏 南京 210000;
    5. 浙江大学医学院附属杭州市第一人民医院 肿瘤外科, 浙江 杭州 310006
  • 发布日期:2020-06-29
  • 通讯作者: 罗定存. E-mail:ldc65@163.com
  • 基金资助:
    杭州市重大科技创新专项项目(20131813A08);杭州市卫生科技计划项目(OO20190490、OO20190151)

Clinical effect of Hashimoto thyroiditis on the ratio of BRAFV600E alleles in papillary thyroid carcinoma

NI Yeqin1, WU Fan1, XUN Yanping2, ZHAO Pan3, ZHANG Shirong2, ZHOU Tianhan1, SUN Sihan4, LU Kaining4, LUO Dingcun5   

  1. 1. The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang, China;
    2. Centre of Translational Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China;
    3. Department of Pathology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang China;
    4. Nanjing Medical University Nanjing 210000, Jiangsu, China;
    5. Department of Surgical Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China;
  • Published:2020-06-29

摘要: 目的 探索桥本甲状腺炎(HT)对甲状腺乳头状癌(PTC)中BRAFV600E突变比值(the ratio of BRAFV600E alleles)的影响。 方法 收集242例PTC患者临床资料,其中PTC合并HT 63例,PTC不合并HT 179例,采用微滴数字PCR(ddPCR)法检测PTC中BRAFV600E状况。利用倾向性评分匹配法(PSM),以性别、年龄、多灶性、腺外侵犯、肿瘤直径为控制变量按1∶1比例构成63对配对,比较匹配后两组BRAFV600E阳性率和突变比值。 结果 倾向性评分匹配前,PTC合并HT组和PTC不合并HT组BRAFV600E阳性率分别为87.3%和92.7%,两组间差异无统计学意义(P>0.05),而PTC合并HT组BRAFV600E突变比值(3.20%)显著低于PTC不合并HT组(8.80%)(P<0.001)。经过倾向性评分匹配,两组基线水平保持一致,PTC合并HT组BRAFV600E突变比值(3.20%)仍显著低于PTC不合并HT组(9.00%),两组间差异有统计学意义(P=0.001)。 结论 在合并HT的PTC中,BRAFV600E突变的发生未受影响,但是BRAFV600E突变比值明显降低,说明HT对PTC发展过程中BRAFV600E突变存在一定影响,从而影响PTC发展及其预后。

关键词: 甲状腺肿瘤, 倾向性评分匹配, 桥本甲状腺炎, BRAFV600E突变比值

Abstract: Objective To evaluate the clinical effect of Hashimoto thyroiditis(HT)on the ratio of BRAFV600E alleles in papillary thyroid carcinoma(PTC). Methods Two hundred and forty-two patients who underwent surgery at our hospital between December 2017 and December 2019 were enrolled in this study. The ratio of BRAFV600E alleles was measured using droplet digital PCR and formalin-fixed paraffin-embedded tissues, and its correlation with HT was analyzed. Using propensity score matching and based on the 63 patients with HT(1∶1), 179 PTC patients without HT during the same period were retrospectively enrolled as controls. Results There was a significant difference between the ratio of BRAFV600E alleles(P<0.001)of the two groups(PTC patients with HT versus those without HT); the rates of positive-BRAFV600E were not significantly different(87.3% vs 92.7%, P>0.05). After propensity score matching, the significant difference between the two groups at baseline was no longer observed. The ratio of BRAFV600E alleles was still significantly lower in patients with HT(median 3.20%)than in those without HT(median 9.00%, P=0.001). Conclusion HT can significantly reduce the ratio of BRAFV600E alleles in PTC, and this has an important effect on PTC progression and prognosis.

Key words: Thyroid neoplasms, Propensity score matching, Hashimoto thyroiditis, Ratio of BRAFV600E alleles

中图分类号: 

  • R604
[1] Xing MZ, 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.
[2] Jankovic B, Le KT, Hershman JM. Clinical Review: Hashimoto's thyroiditis and papillary thyroid carcinoma: is there a correlation?[J]. J Clin Endocrinol Metab, 2013, 98(2): 474-482. doi:10.1210/jc.2012-2978.
[3] Golden SH, Robinson KA, Saldanha I, et al. Clinical review: Prevalence and incidence of endocrine and metabolic disorders in the United States: a comprehensive review[J]. J Clin Endocrinol Metab, 2009, 94(6): 1853-1878. doi:10.1210/jc.2008-2291.
[4] Lee YK, Park KH, Park SH, et al. Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation[J]. Head Neck, 2018, 40(10): 2271-2279. doi:10.1002/hed.25327.
[5] Kwak HY, Chae BJ, Eom YH, et al. Does papillary thyroid carcinoma have a better prognosis with or without Hashimoto thyroiditis?[J]. Int J Clin Oncol, 2015, 20(3): 463-473. doi:10.1007/s10147-014-0754-7.
[6] Zhang Q, Liu BJ, Ren WW, et al. Association between BRAFV600E mutation and ultrasound features in papillary thyroid carcinoma patients with and without hashimoto's thyroiditis[J]. Sci Rep, 2017, 7(1): 4899. doi:10.1038/s41598-017-05153-y.
[7] Marotta V, Guerra A, Zatelli MC, et al. BRAF mutation positive papillary thyroid carcinoma is less advanced when Hashimoto's thyroiditis lymphocytic infiltration is present[J]. Clin Endocrinol(Oxf), 2013, 79(5): 733-738. doi:10.1111/cen.12194.
[8] Ylli D, Patel A, Jensen K, et al. Microfluidic droplet digital PCR is a powerful tool for detection of BRAF and TERT mutations in papillary thyroid carcinomas[J]. Cancers(Basel), 2019, 11(12): E1916. doi:10.3390/cancers11121916.
[9] 倪烨钦, 荀延萍, 赵盼,等. BRAFV600E突变比值在预测甲状腺乳头状癌颈部淋巴结转移中的临床价值[J]. 国际耳鼻咽喉头颈外科杂志. 2020, 44(1):6-10. doi:10.3760/cma.j.issn.1673-4106.2020.01.002 NI Yeqin, XUN Yanping, ZHAO Pan, et al. Clinical value of the ratio of BRAFV600E expression for predicting lymph node metastasis in papillary thyroid carcinoma[J]. International Journal of Dermatology and Venereology, 2020, 44(1):6-10. doi:10.3760/cma.j.issn.1673-4106.2020.01.002
[10] Guan HX, de Morais NS, Stuart J, et al. Discordance of serological and sonographic markers for Hashimoto's thyroiditis with gold standard histopathology[J]. Eur J Endocrinol, 2019, 181(5): 539-544. doi:10.1530/EJE-19-0424.
[11] 中华医学会内分泌学分会《中国甲状腺疾病诊治指南》编写组. 中国甲状腺疾病诊治指南——甲状腺炎:亚急性甲状腺炎[J]. 中华内科杂志. 2008, 47(9):784-785.
[12] Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects[J]. Biometrika, 1983, 70(1): 41-55. doi:10.1093/biomet/70.1.41.
[13] Lee JH, Kim Y, Choi JW, et al. The association between papillary thyroid carcinoma and histologically proven Hashimoto's thyroiditis: a meta-analysis[J]. Eur J Endocrinol, 2013, 168(3): 343-349. doi:10.1530/EJE-12-0903.
[14] Liang J, Zeng W, Fang F, et al. Clinical analysis of Hashimoto thyroiditis coexistent with papillary thyroid cancer in 1392 patients[J]. Acta Otorhinolaryngol Ital, 2017, 37(5): 393-400. doi:10.14639/0392-100X-1709.
[15] Riesco-Eizaguirre G, Rodríguez I, De la Vieja A, et al. The BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer[J]. Cancer Res, 2009, 69(21): 8317-8325. doi:10.1158/0008-5472.CAN-09-1248.
[16] Xing MZ, 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.
[17] Kimura ET, Nikiforova MN, Zhu ZW, et al. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma[J]. Cancer Res, 2003, 63(7): 1454-1457.
[18] Xing M. BRAF mutation in thyroid cancer[J]. Endocr Relat Cancer, 2005, 12(2): 245-262. doi:10.1677/erc.1.0978.
[19] Li XY, Li EL, Du J, et al. BRAF mutation analysis by ARMS-PCR refines thyroid nodule management[J]. Clin Endocrinol(Oxf), 2019, 91(6): 834-841. doi:10.1111/cen.14079.
[20] Ren HY, Shen YF, Hu DX, et al. Co-existence of BRAFV600E and TERT promoter mutations in papillary thyroid carcinoma is associated with tumor aggressiveness, but not with lymph node metastasis[J]. Cancer Manag Res, 2018, 10: 1005-1013. doi:10.2147/CMAR.S159583.
[21] Olmedillas-López S, García-Arranz M, García-Olmo D. Current and emerging applications of droplet digital PCR in oncology[J]. Mol Diagn Ther, 2017, 21(5): 493-510. doi:10.1007/s40291-017-0278-8.
[22] Muzza M, Degl'Innocenti D, Colombo C, et al. The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies[J]. Clin Endocrinol(Oxf), 2010, 72(5): 702-708. doi:10.1111/j.1365-2265.2009.03699.x.
[23] Colombo C, Muzza M, Proverbio MC, et al. Impact of mutation density and heterogeneity on papillary thyroid cancer clinical features and remission probability[J]. Thyroid, 2019, 29(2): 237-251. doi:10.1089/thy.2018.0339.
[24] Guerra A, Sapio MR, Marotta V, et al. The primary occurrence of BRAF(V600E)is a rare clonal event in papillary thyroid carcinoma[J]. J Clin Endocrinol Metab, 2012, 97(2): 517-524. doi:10.1210/jc.2011-0618.
[1] 宋晓宇,宋西成. 缺氧诱导因子-1α在甲状腺癌中的调节机制[J]. 山东大学耳鼻喉眼学报, 2019, 33(2): 136-138.
[2] 高晓倩,姜震,耿琛琛,刘大昱,李荔. 术前超声评估分化型甲状腺癌颈部淋巴结转移[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 135-139.
[3] 房居高. 强化手术技能和规范诊疗是提高甲状腺癌疗效的根本[J]. 山东大学耳鼻喉眼学报, 2016, 30(2): 1-4.
[4] 龚单春,张海东,张庆翔,何双八,于振坤. 精细化甲状腺腺叶切除操作技术[J]. 山东大学耳鼻喉眼学报, 2016, 30(2): 5-9.
[5] 王宇,马奔. 超声引导下热消融技术尚不适用于甲状腺癌及甲状腺滤泡性肿瘤治疗[J]. 山东大学耳鼻喉眼学报, 2016, 30(2): 20-22.
[6] 陈晓红. 遗传型甲状腺髓样癌的精准化治疗[J]. 山东大学耳鼻喉眼学报, 2016, 30(2): 23-27.
[7] 徐增瑞, 张建新, 石继红, 蔡晓岚. 异种脱细胞真皮基质修复膜修复甲状腺癌切除术后气管缺损13例[J]. 山东大学耳鼻喉眼学报, 2015, 29(5): 52-54.
[8] 庄大勇,贺青卿,范子义,郑鲁明,朱见,周鹏,段松建,岳涛,董学峰. 术中神经监测技术在分化型甲状腺癌再次手术中的应用[J]. 山东大学耳鼻喉眼学报, 2013, 27(6): 5-8.
[9] 刘新义,刘 艳,李颂军,李大建,薛令军 . 甲状腺微小癌的临床特征及早期诊断[J]. 山东大学耳鼻喉眼学报, 2008, 22(1): 29-31 .
[10] 赵雪柠,叶 萍 综述, 潘新良,雷大鹏 审校 . 晚期甲状腺癌累及喉、气管和食管的外科治疗[J]. 山东大学耳鼻喉眼学报, 2007, 21(3): 260-262 .
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!