甲状腺乳头状癌常规超声特征及相关因素与BRAFV600E基因突变的相关性

吕阳; 何秀丽; 杨芳; 郭玲玲; 祁明; 张洁; 王欢

doi:10.13201/j.issn.2096-7993.2021.10.013

甲状腺乳头状癌常规超声特征及相关因素与BRAFV600E基因突变的相关性

- 1.
  锦州医科大学附属第一医院超声科(辽宁锦州，121000)
- 2.
  鞍山市中心医院超声科
- 3.
  锦州医科大学附属第一医院甲状腺外科

详细信息

通讯作者: 何秀丽, E-mail: hexiuli69737@sina.com

中图分类号: R736.1

收稿日期: 2021-07-17

刊出日期: 2021-10-05

Correlation of conventional ultrasound features and related factors with BRAFV600E gene mutation in papillary thyroid carcinoma

- 1.
  Department of Ultrasound, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China
- 2.
  Department of Ultrasound, Anshan Central Hospital
- 3.
  Department of Thyroid Surgery, First Affiliated Hospital of Jinzhou Medical University

More Information

Corresponding author: HE Xiuli, E-mail: hexiuli69737@sina.com

Received Date: 17 July 2021

Publish Date: 05 October 2021

摘要

摘要: 目的探讨甲状腺乳头状癌(PTC)的常规超声特征及相关因素与BRAFV600E基因突变的相关性。方法选取2019年10月—2021年3月经锦州医科大学附属第一医院手术病理证实的208例PTC患者共266个结节, 术后均采用实时荧光PCR定量技术行BRAFV600E基因检测, 根据基因检测结果分为基因突变阳性组和阴性组, 收集患者的常规超声特征及临床资料, 分析其与BRAFV600E基因突变的相关性。结果 266个样本中, 188例(70.7%)发生基因突变。单因素分析结果显示: 两组患者年龄、结节边缘、与被膜分界、微钙化、颈部异常淋巴结等指标差异有统计学意义(P < 0.05)。Logistic多因素回归分析结果显示: 年龄、结节边缘、颈部异常淋巴结为PTC患者BRAFV600E基因突变的独立影响因素(P < 0.05)。ROC曲线显示: 当年龄取值为46.5岁时, 约登指数为最大值。结论 PTC患者BRAFV600E基因突变与年龄≤46.5岁、结节边缘不光整、颈部存在异常淋巴结存在相关性, 上述特征可以用来评估BRAFV600E基因突变情况, 对临床诊疗及预后评估有一定的指导意义。
- 甲状腺肿瘤 /
- 乳头状癌 /
- BRAFV600E基因 /
- 超声特征
Abstract: Objective To investigate the correlation of conventional ultrasound features and related factors with BRAFV600E gene mutation in papillary thyroid carcinoma(PTC).Methods A total of 266 nodules in 208 patients with PTC confirmed by operation and pathology in First Affiliated Hospital of Jinzhou Medical University from October 2019 to March 2021 were selected. BRAFV600E gene was detected by real-time fluorescence PCR quantitative technique after operation. According to the results of gene detection, the patients were divided into gene mutation positive group and gene mutation negative group. The routine ultrasound features and clinical data of the patients were collected, and the correlation with BRAFV600E gene mutation was analyzed.Results Among the 266 samples, 188 cases(70.7%) had gene mutation. Univariate analysis showed that there were significant differences in age, nodular edge, capsule boundary, microcalcification and abnormal cervical lymph nodes between the two groups(P < 0.05). The results of Logistic multivariate regression analysis showed that age, nodular margin and abnormal cervical lymph nodes were independent influencing factors of BRAFV600E gene mutation in patients with PTC. ROC curve showed that when the age was 46.5 years old, the Youden index was the highest.Conclusion BRAFV600E gene mutation is associated with age≤46.5 years old, uneven edge of nodules and abnormal lymph nodes in neck in patients with PTC. The above characteristics can be used to evaluate BRAFV600E gene mutation and have certain guiding significance for clinical diagnosis, treatment and prognosis.
- thyroid neoplasms /
- papillary carcinoma /
- BRAFV600E gene /
- ultrasonographic features

HTML全文

图 1 发生BRAFV600E基因突变的PTC患者的超声图像

下载: 全尺寸图片幻灯片

图 2 年龄的ROC曲线

下载: 全尺寸图片幻灯片

表 1 PTC患者超声特征及相关因素与BRAFV600E基因突变分析

研究因素	阳性组 (n=188)	阴性组 (n=78)	χ²/t	P	研究因素	阳性组 (n=188)	阴性组 (n=78)	χ²/t	P
年龄/岁	41±10	51±9	7.316	< 0.01	结节边缘
性别					不光整	183(75.3)	60(24.7)	29.094	< 0.01
男	48(77.4)	14(22.6)	1.773	>0.05	光整	5(21.7)	18(78.3)	29.094	< 0.01
女	140(68.6)	64(31.4)	1.773	>0.05	与被膜分界
结节数目/个					不清	111(78.2)	31(21.8)	8.251	< 0.01
1	108(69.2)	48(30.8)	0.381	>0.05	清晰	77(62.1)	47(37.9)	8.251	< 0.01
≥2	80(72.7)	30(27.3)	0.381	>0.05	结节形态(纵横比)
最大径线/mm	9.3±6.1	9.3±4.5	0.028	>0.05	>1	141(73.4)	51(26.6)	2.538	>0.05
回声性质					< 1	47(63.5)	27(36.5)	2.538	>0.05
极低回声	36(80.0)	9(20.0)			微钙化
低回声	135(68.2)	63(31.8)	2.598	>0.05	有	89(79.5)	23(20.5)	7.208	< 0.01
等回声	17(73.9)	6(26.1)			无	99(64.3)	55(35.7)	7.208	< 0.01
结构性质					颈部异常淋巴结
实性	180(70.3)	76(29.7)	0.414	>0.05	有	100(83.3)	20(16.7)	16.899	< 0.01
囊实性	8(80.0)	2(20.0)	0.414	>0.05	无	88(60.3)	58(39.7)	16.899	< 0.01

下载: 导出CSV

表 2 多因素Logistic回归分析BRAFV600E基因突变的危险因素

研究因素	回归系数(β)	标准误	Wald	P	OR	95%CI
年龄	1.051	0.342	9.431	< 0.01	2.859	1.462~5.591
结节边缘	2.182	0.561	15.133	< 0.01	8.862	2.952~26.601
与被膜分界	0.308	0.307	1.009	>0.05	1.361	0.746~2.484
微钙化	0.554	0.319	3.002	>0.05	1.739	0.930~3.253
颈部异常淋巴结	0.911	0.323	7.951	< 0.01	2.487	1.320~4.685

下载: 导出CSV

参考文献(18)

[1]	Durante C, Grani G, Lamartina L, et al. The Diagnosis and Management of Thyroid Nodules: A Review[J]. JAMA, 2018, 319(9): 914-924. doi: 10.1001/jama.2018.0898
[2]	Huang M, Yan C, Wei H, et al. Clinicopathological characteristics and prognosis of thyroid cancer in northwest China: A population-based retrospective study of 2490 patients[J]. Thorac Cancer, 2018, 9(11): 1453-1460. doi: 10.1111/1759-7714.12858
[3]	Abdullah MI, Junit SM, Ng KL, et al. Papillary Thyroid Cancer: Genetic Alterations and Molecular Biomarker Investigations[J]. Int J Med Sci, 2019, 16(3): 450-460. doi: 10.7150/ijms.29935
[4]	Collet JF, Lacave R, Hugonin S, et al. BRAF V600E detection in cytological thyroid samples: A key component of the decision tree for surgical treatment of papillary thyroid carcinoma[J]. Head Neck, 2016, 38(7): 1017-1021. doi: 10.1002/hed.24393
[5]	Jinih M, Foley N, Osho O, et al. BRAFV600E mutation as a predictor of thyroid malignancy in indeterminate nodules: A systematic review and meta-analysis[J]. Eur J Surg Oncol, 2017, 43(7): 1219-1227. doi: 10.1016/j.ejso.2016.11.003
[6]	Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer[J]. Thyroid, 2016, 26(1): 1-133. doi: 10.1089/thy.2015.0020
[7]	Jat MA. Comparison of surgeon-performed ultrasound-guided fine needle aspiration cytology with histopathological diagnosis of thyroid nodules[J]. Pak J Med Sci, 2019, 35(4): 1003-1007.
[8]	王丽荟, 陈路增, 高莹, 等. 超声引导下甲状腺结节粗针穿刺活检与细针抽吸取材满意率比较[J]. 中国超声医学杂志, 2017, 33(3): 199-202. doi: 10.3969/j.issn.1002-0101.2017.03.003
[9]	中华医学会超声医学分会浅表器官和血管学组, 中国甲状腺与乳腺超声人工智能联盟. 2020甲状腺结节超声恶性危险分层中国指南: C-TIRADS[J]. 中华超声影像学杂志, 2021, 30(3): 185-200. doi: 10.3760/cma.j.cn131148-20210205-00092
[10]	Kure S, Ishino K, Kudo M, et al. Incidence of BRAF V600E mutation in patients with papillary thyroid carcinoma: a single-institution experience[J]. J Int Med Res, 2019, 47(11): 5560-5572. doi: 10.1177/0300060519873481
[11]	Yan C, Huang M, Li X, et al. Relationship between BRAF V600E and clinical features in papillary thyroid carcinoma[J]. Endocr Connect, 2019, 8(7): 988-996. doi: 10.1530/EC-19-0246
[12]	王成晨, 向大鹏, 李志宇. 甲状腺乳头状癌相关基因突变与其临床病理特征的关系[J]. 实用肿瘤杂志, 2019, 34(3): 239-244. https://www.cnki.com.cn/Article/CJFDTOTAL-SYZZ201903012.htm
[13]	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. doi: 10.1038/s41598-017-05153-y
[14]	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492
[15]	Chen B, Zhang Z, Wang K, et al. Association of BRAFV600E mutation with ultrasonographic features and clinicopathologic characteristics of papillary thyroid microcarcinoma: A retrospective study of 116 cases[J]. Clin Hemorheol Microcirc, 2019, 73(4): 545-552.
[16]	王国涛, 黎燕, 梁瑾瑜, 等. 甲状腺乳头状癌BRAF V600E基因突变与临床及超声特征的相关性研究[J]. 中国超声医学杂志, 2021, 37(4): 376-379. doi: 10.3969/j.issn.1002-0101.2021.04.005
[17]	单云云, 彭梅, 张新书, 等. 甲状腺乳头状癌中BRAF^V600E基因突变与超声声像图的相关性研究[J]. 中国超声医学杂志, 2017, 33(10): 868-870. doi: 10.3969/j.issn.1002-0101.2017.10.002
[18]	郭荣荣, 郭江红, 兰慧娟, 等. 甲状腺癌超声特征与BRAF V600E基因突变相关性分析[J]. 肿瘤研究与临床, 2020, 32(9): 622-627. doi: 10.3760/cma.j.cn115355-20191126-00534