Progress of BRAF V600E mutation and papillary thyroid carcinoma
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摘要: 甲状腺乳头状癌(PTC)起源于甲状腺滤泡上皮细胞,预后一般较好。但近年来PTC的发病率急剧上升,严重影响公众健康,甲状腺乳头状癌常被分为几种亚型:经典型、滤泡亚型、高细胞亚型、平头钉亚型及弥漫硬化型等,不同亚型的侵袭性有所不同。BRAF V600E突变是甲状腺乳头状癌的最常见的分子标志物,也是近年来的分子研究热点,和PTC的发生发展机制、侵袭性及预后密切相关。随着BRAF V600E突变研究的不断深入,关于它与PTC之间关系的矛盾点及争论点慢慢浮现,本文就近5年来的相关文献进行综述,主要从BRAF V600E突变与PTC的作用发生机制、临床病理特征关系、预后、指导临床治疗及相关基因联合等方面进行阐述,并针对当前的争议点及矛盾点进行比较分析。
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关键词:
- 甲状腺乳头状癌 /
- BRAF V600E突变 /
- 侵袭性 /
- 预后标志物
Abstract: Papillary thyroid carcinoma originated in thyroid follicular epithelial cells, the prognosis is generally better. However, the incidence of PTC has risen sharply in recent years, seriously affecting public health. Papillary thyroid carcinoma is often divided into several subtypes: Classical, Follicular-variant, Tall cell subtype, Hobnail variant and Diffuse sclerosis, et al. The aggressiveness of different subtypes is different. BRAFV600E mutation is the most common molecular marker of papillary thyroid carcinoma and is also a hot spot in molecular research in recent years. It is closely related to the occurrence, development mechanism, invasion and prognosis of PTC. With the deepening of BRAF V600E mutation research and its contradictory points and controversies about the relationship between PTC and BRAF V600E, this review summarizes the relevant literature in the recent five years mainly from the mechanisms of BRAF V600E mutation and PTC, the clinicopathological features relationship, prognosis, guiding clinical treatment and related gene combination and so on. The dissertation analyzes the controversial and contradictory points in current literatures.-
Key words:
- thyroid papillary carcinoma /
- BRAF V600E mutation /
- nvasivenessi /
- prognostic marker
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[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30 doi: 10.3322/caac.v68.1 [2] Davies L, Welch HG. Current thyroid cancer trends in the United States[J]. JAMA Otolaryngol Head Neck Surg, 2014, 140(4): 317-22 doi: 10.1001/jamaoto.2014.1 [3] Xing M. BRAF mutation in thyroid cancer[J]. Endocr Relat Cancer, 2005, 12(2): 245-8 doi: 10.1677/erc.1.0978 [4] Liu C, Chen T, Liu Z. Associations between BRAF(V600E) and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis[J]. World J Surg Oncol, 2016, 14(1): 241-5 doi: 10.1186/s12957-016-0979-1 [5] Lu J, Gao J, Zhang J, et al. Association between BRAF V600E mutation and regional lymph node metastasis in papillary thyroid carcinoma[J]. Int J Clin Exp Pathol, 2015, 8(1): 793-9 [6] 徐晓琴, 王旭红, 荆结线. BRAFV600E基因突变与甲状腺乳头状癌的相关性研究进展[J]. 中华耳鼻咽喉头颈外科杂志, 2016, 51(8): 630-4 doi: 10.3760/cma.j.issn.1673-0860.2016.08.016 [7] Xing MZ. Molecular pathogenesis and mechanisms of thyroid cancer[J]. Nat Rev Cancer, 2013, 13(3): 184-99 doi: 10.1038/nrc3431 [8] Orim F, Bychkov A, Shimamura M, et al. Thyrotropin signaling confers more aggressive features with higher genomic instability on BRAF(V600E)-induced thyroid tumors in a mouse model[J]. Thyroid, 2014, 24(3): 502-10 doi: 10.1089/thy.2013.0038 [9] Khan MS, Pandith AA, Masoodi SR, et al. Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their BRAF V600E mutation status[J]. Endocrine, 2014, 47(2): 449-55 doi: 10.1007/s12020-014-0319-6 [10] 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): 8317-25 doi: 10.1158/0008-5472.CAN-09-1248 [11] Zhang Z, Liu D, Murugan AK, et al. Histone deacetylation of NIS promoter underlies BRAF V600E-promoted NIS silencing in thyroid cancer[J]. Endocr Relat Cancer, 2014, 21(2): 161-73 [12] Jeong D, Jeong Y, Park JH, et al. BRAF (V600E) mutation analysis in papillary thyroid carcinomas by peptide nucleic acid clamp real-time PCR[J]. Ann Surg Oncol, 2013, 20(3): 759-66 doi: 10.1245/s10434-012-2494-0 [13] Navarro-Locsin CG, Chang AM, Daroy ML, et al. Clinical and histopathological profile of BRAF V600E mutation in conventional papillary thyroid carcinoma in a Filipino population[J]. Malays J Pathol, 2016, 38(2): 141-8 [14] Alzahrani AS, Murugan AK, Qasem E, et al. Single point mutations in pediatric differentiated thyroid cancer[J]. Thyroid, 2017, 27(2): 189-96 doi: 10.1089/thy.2016.0339 [15] Choi SY, Park H, Kang MK, et al. The relationship between the BRAF(V600E) mutation in papillary thyroid microcarcinoma and clinicopathologic factors[J]. World J Surg Oncol, 2013, 11(1): 291-7 doi: 10.1186/1477-7819-11-291 [16] Lim JY, Hong SW, Lee YS, et al. Clinicopathologic implications of the BRAF(V600E) mutation in papillary thyroid cancer: a subgroup analysis of 3130 cases in a single center[J]. Thyroid, 2013, 23(11): 1423-30 doi: 10.1089/thy.2013.0036 [17] Virk RK, Van Dyke AL, Finkelstein AA, et al. BRAF(V600E) mutation in papillary thyroid microcarcinoma: a genotype-phenotype correlation[J]. Modern Pathology, 2013, 26(1): 62-70 doi: 10.1038/modpathol.2012.152 [18] Bernstein J, Virk RK, Hui P, et al. Tall cell variant of papillary thyroid microcarcinoma: clinicopathologic features with BRAF(V600E) mutational analysis[J]. Thyroid, 2013, 23(12): 1525-31 doi: 10.1089/thy.2013.0154 [19] Liu X, Yan K, Lin X, et al. The association between BRAF (V600E) mutation and pathological features in PTC[J]. Eur Arch Otorhinolaryngol, 2014, 271(11): 3041-52 doi: 10.1007/s00405-013-2872-7 [20] Shin DY, Kim KJ, Chang S, et al. Follicular variant of papillary thyroid carcinoma with B-type Raf(V600E) showing higher frequency of suspicious sonographic features and multifocality[J]. Head Neck, 2015, 37(11): 1590-5 doi: 10.1002/hed.v37.11 [21] Ahn HY, Chung YJ, Kim BS, et al. Clinical significance of the BRAF V600E mutation in multifocal papillary thyroid carcinoma in Korea[J]. Surgery, 2014, 155(4): 689-95 doi: 10.1016/j.surg.2013.12.025 [22] Phd EM, Phd MM, Sara CD, 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): 291-7 doi: 10.1002/cncy.21258 [23] Yu L, Ma L, Tu Q, et al. Clinical significance of BRAF V600E mutation in 154 patients with thyroid nodules[J]. Oncol Lett, 2015, 9(6): 2633-8 doi: 10.3892/ol.2015.3119 [24] Howell GM, Nikiforova MN, Carty SE, et al. BRAF V600E mutation independently predicts central compartment lymph node metastasis in patients with papillary thyroid cancer[J]. Ann Surg Oncol, 2013, 20(1): 47-52 doi: 10.1245/s10434-012-2611-0 [25] Gandolfi G, Sancisi V, Torricelli F, et al. Allele percentage of the BRAF V600E mutation in papillary thyroid carcinomas and corresponding lymph node metastases: no evidence for a role in tumor progression[J]. J Clin Endocrinol Metab, 2013, 98(5): E934-42 doi: 10.1210/jc.2012-3930 [26] Gouveia C, Can NT, Bostrom A, et al. Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience[J]. JAMA Otolaryngol Head Neck Surg, 2013, 139(11): 1164-70 doi: 10.1001/jamaoto.2013.4501 [27] Liu S, Zhang B, Zhao Y, et al. Association of BRAFV600E mutation with clinicopathological features of papillary thyroid carcinoma: a study on a Chinese population[J]. Int J Clin Exp Pathol, 2014, 7(10): 6922-8 [28] Cheng SP, Hsu YC, Liu CL, et al. Significance of allelic percentage of BRAF c.1799T > A (V600E) mutation in papillary thyroid carcinoma[J]. Ann Surg Oncol, 2014, 21(Suppl 4): S619-26 [29] Jing FJ, Liang J, Liang ZY, et al. BRAF(V600E)mutation is not a positive predictor for distant metastasis in sporadic papillary thyroid carcinoma[J]. J Chin Med, 2013, 126(16): 3013-8 [30] Givens DJ, Buchmann LO, Agarwal AM, et al. BRAF V600E does not predict aggressive features of pediatric papillary thyroid carcinoma[J]. Laryngoscope, 2014, 124(9): E389-93 doi: 10.1002/lary.24668 [31] Kim BH, Kim IJ, Lee BJ, et al. Detection of plasma BRAF(V600E) mutation is associated with lung metastasis in papillary thyroid carcinomas[J]. Yonsei Med J, 2015, 56(3): 634-40 doi: 10.3349/ymj.2015.56.3.634 [32] Bastos AU, Oler G, Nozima BH, et al. BRAF V600E and decreased NIS and TPO expression are associated with aggressiveness of a subgroup of papillary thyroid microcarcinoma[J]. Europ J Endocrinol, 2015, 173(4): 525-40 doi: 10.1530/EJE-15-0254 [33] Kim SK, Lee JH, Woo JW, et al. BRAF V600E mutation: Differential impact on central lymph node metastasis by tumor size in papillary thyroid carcinoma[J]. Head Neck, 2016, 38(Suppl 1): E1203-9 [34] Henke LE, Perkins SM, Pfeifer JD, et al. BRAF V600E mutational status in pediatric thyroid cancer[J]. Pediatr Blood Cancer, 2014, 61(7): 1168-72 doi: 10.1002/pbc.24935 [35] Kim SJ, Myong JP, Jee HG, et al. Combined effect of Hashimoto's thyroiditis and BRAF(V600E) mutation status on aggressiveness in papillary thyroid cancer[J]. Head Neck, 2016, 38(1): 95-101 doi: 10.1002/hed.23854 [36] Zeng RC, Jin LP, Chen ED, et al. Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer[J]. Head Neck, 2016, 38(Suppl 1): E1019-25 [37] He G, Zhao B, Zhang X, et al. Prognostic value of the BRAF V600E mutation in papillary thyroid carcinoma[J]. Oncol Lett, 2014, 7(2): 439-43 doi: 10.3892/ol.2013.1713 [38] Xing M, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and recurrence of papillary thyroid cancer[J]. J Clin Oncol, 2015, 33(1): 42-50 doi: 10.1200/JCO.2014.56.8253 [39] Mckelvie PA, Chan F, Yu Y, et al. The prognostic significance of the BRAF V600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry[J]. Pathology, 2013, 45(7): 637-44 doi: 10.1097/PAT.0000000000000008 [40] Dağlar-Aday A, Toptaş B, Oztürk T, et al. Investigation of BRAF V600E mutation in papillary thyroid carcinoma and tumor-surrounding nontumoral tissues[J]. DNA Cell Biol, 2013, 32(1): 13-8 doi: 10.1089/dna.2012.1776 [41] Czarniecka A, Kowal M, Rusinek D, et al. The risk of relapse in papillary thyroid cancer (PTC) in the context of BRAFV600E mutation status and other prognostic factors[J]. PLoS One, 2015, 10(7): e0132821-6 doi: 10.1371/journal.pone.0132821 [42] Xing MZ, Alzahrani AS, Carson KA, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer[J]. JAMA, 2013, 309(14): 1493-501 doi: 10.1001/jama.2013.3190 [43] Russo M, Malandrino P, Nicolosi ML, et al. The BRAF(V600E) mutation influences the short- and medium-term outcomes of classic papillary thyroid cancer, but is not an Independent predictor of unfavorable outcome[J]. Thyroid, 2014, 24(8): 1267-74 doi: 10.1089/thy.2013.0675 [44] Zhang Q, Liu BJ, Ren WW, et al. Association between BRAF V600E Mutation and Ultrasound Features in Papillary Thyroid Carcinoma Patients with and without Hashimoto's Thyroiditis[J]. Sci Rep, 2017, 7(1): 4899-104 doi: 10.1038/s41598-017-05153-y [45] Li Q, Yuan J, Wang Y, et al. Association between the BRAF V600E mutation and ultrasound features of the thyroid in thyroid papillary carcinoma[J]. Oncol Lett, 2017, 14(2): 1439-44 doi: 10.3892/ol.2017.6276 [46] Chang JW, Park KW, Heo JH, et al. Relationship between 18f-fluorodeoxyglucose accumulation and the BRAF V600E mutation in papillary thyroid cancer[J]. World J Surg, 2018, 42(1): 114-22 doi: 10.1007/s00268-017-4136-y [47] Zhao H, Zhang ZH, Zhou B, et al. Detection of BRAF c.1799T > A (p.V600E) mutation using residual routine fine-needle aspiration specimens of papillary thyroid carcinoma[J]. Diagn Cytopathol, 2015, 43(10): 786-90 doi: 10.1002/dc.v43.10 [48] Fu QF, Pan PT, Zhou L, et al. Clinical significance of preoperative detection of serum p53 antibodies and BRAF(V600E) mutation in patients with papillary thyroid carcinoma[J]. Int J Clin Exp Med, 2015, 8(11): 21327-34 [49] Lee JW, Koo BS. The prognostic implication and potential role of BRAF mutation in the decision to perform elective neck dissection for thyroid cancer[J]. Gland surgery, 2013, 2(4): 206-11 [50] 石臣磊, 郭 勇, 吕一辰, 等. 适合手术的甲状腺微小乳头状癌患者临床病理特征[J]. 中华肿瘤杂志, 2017, 39(5): 361-6 doi: 10.3760/cma.j.issn.0253-3766.2017.05.008 [51] Pelizzo MR, Dobrinja C, Ide EC, et al. The role of BRAF(V600E) mutation as poor prognostic factor for the outcome of patients with intrathyroid papillary thyroid carcinoma[J]. Biomed Pharmacoth, 2014, 68(4): 413-7 doi: 10.1016/j.biopha.2014.03.008 [52] Han SA, Park WS, Jang JH, et al. BRAF mutation May predict higher necessity of postoperative radioactive Iodine ablation in papillary thyroid cancer[J]. Annal Surg Treatm Res, 2014, 87(4): 174-9 doi: 10.4174/astr.2014.87.4.174 [53] 李 娇, 杨 涛, 赵 腾, 等. BRAF~(V600E)突变性中低危甲状腺乳头状癌患者~(131)I治疗疗效评价[J]. 中国医学科学院学报, 2016, 38(3): 346-50 doi: 10.3881/j.issn.1000-503X.2016.03.019 [54] 林岩松, 杨雪. 碘难治性甲状腺癌的诊治进展[J]. 中国癌症杂志, 2017, 27(6): 442-50 [55] Brose MS, Nutting CM, Jarzab BA, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial[J]. Lancet, 2014, 384(9940): 319-28 doi: 10.1016/S0140-6736(14)60421-9 [56] Falchook GS, Millward M, Hong D, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer[J]. Thyroid, 2015, 25(1): 71-7 doi: 10.1089/thy.2014.0123 [57] Liu X, Qu S, Liu R, et al. TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer[J]. J Clin Endocrinol Metab, 2014, 99(6): E1130-6 doi: 10.1210/jc.2013-4048 [58] Xing M, Liu R, Liu X, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence[J]. J Clin Oncol, 2014, 32(25): 2718-26 doi: 10.1200/JCO.2014.55.5094 [59] Zou M, Baitei EY, Alzahrani AS, et al. Concomitant RAS, RET/PTC, or BRAF mutations in advanced stage of papillary thyroid carcinoma[J]. Thyroid, 2014, 24(8): 1256-66 doi: 10.1089/thy.2013.0610 [60] 孟 超, 高 洁, 梁 军, 等. 甲状腺乳头状癌并BRAF~(V600E)突变及原癌基因重排蛋白表达与其侵袭性的关系[J]. 中国医学科学院学报, 2013, 35(1): 64-8 doi: 10.3881/j.issn.1000-503X.2013.01.012
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