细针穿刺活检联合高通量测序技术在甲状腺结节诊疗中的应用

doi:10.3969/j.issn.1006-5725.2024.17.020

Abstract

Abstract:

Objective To investigate the role and clinical significance of fine-needle aspiration combined with next-generation sequencing 18 genes detection in the diagnosis of thyroid cancer. Methods The samples were tested by liquid-based cytology and next-generation sequencing. Cytological diagnosis was based on the 3rd edition Bethesda system for reporting thyroid cytopathology. Histological diagnosis was based on the fifth WHO classification criteria for thyroid neoplasms. Results Among 97 thyroid specimens， 8 cases （8.25%） were unsatisfied， 44 cases （45.36%） had benign lesions， 9 cases （9.28%） had atypical cells of unknown significance， 4 cases （4.12%） had suspected follicular or oncocytic tumors. Suspected papillary carcinoma was found in 10 cases （10.31%） and papillary carcinoma in 22 cases （22.68%）. A total of 52 cases （53.61%） were mutated， and 10 gene mutations were detected， among which BRAF gene mutation had the highest detection rate 63.46% （33/52）. BRAF gene mutation was associated with gender， age and cytological diagnosis（P < 0.05）. Cytology combined with next-generation sequencing improved the diagnostic accuracy （97.0% vs. 81.8%）， having higher diagnostic efficiency. Conclusion Thyroid fine-needle aspiration cytology combined with next-generation sequencing can promote early diagnosis of thyroid cancer and provide basis for individual treatment of patients.

Key words: fine needle aspiration, next-generation sequencing, gene mutation, thyroid cancer

CLC Number:

R736.1

Feng ZHU,Qing LI,Xi CHEN,Yang HE,Lei. PENG. Application of FNA combined with next⁃generation sequencing in the diagnosis and treatment of thyroid nodules[J]. The Journal of Practical Medicine, 2024, 40(17): 2471-2476.

Figures/Tables 5

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References 32

1	WILTSHIRE J J， DRAKE T M， UTTLEY L， et al. Systematic review of trends in the incidence rates of thyroid cancer［J］. Thyroid， 2016， 26（11）：1541-1552. doi:10.1089/thy.2016.0100 doi: 10.1089/thy.2016.0100
2	HUANG F， WANG L， JIA H. Research trends for papillary thyroid carcinoma from 2010 to 2019： A systematic review and bibliometrics analysis［J］. Medicine （Baltimore）， 2021， 100（21）：e26100. doi:10.1097/md.0000000000026100 doi: 10.1097/md.0000000000026100
3	SIEGEL R L， MILLER K D， WAGLE N S， et al. Cancer statistics［J］. CA Cancer J Clin， 2023， 73（1）：17-48. doi:10.3322/caac.21763 doi: 10.3322/caac.21763
4	BALOCH Z W， ASA S L， BARLETTA J A， et al. Overview of the 2022 WHO Classification of Thyroid Neoplasms［J］. Endocr Pathol， 2022， 33（1）：27-63. doi:10.1007/s12022-022-09707-3 doi: 10.1007/s12022-022-09707-3
5	ALI S Z， BALOCH Z W， COCHAND-PRIOLLET B， et al. The 2023 Bethesda System for ReportingThyroid Cytopathology［J］.Thyroid， 2023，33（9）：1039-1044.
6	DUMAN B B， KARA O J， UGUZ A， et al. Evaluation of PTEN， Pl3K， MTOR and KRAS expression and their clinical and prognostic relevance to differentiated thyroid carcinoma［J］. Contemp Oncol （Pozn）， 2014， 18（4）：234-240.
7	PRASAD M L， VYAS M， HORNE M J， et al. NTRK fusion oncogenes in pediatric papillary thyroid carcinoma in northeast United States［J］. Cancer， 2016， 122 （7）：1097-1107. doi:10.1002/cncr.29887 doi: 10.1002/cncr.29887
8	DERWICH A， SYKUTERA M， BROMINSKA B， et al. Clinical Implications of mTOR Expression in Papillary Thyroid Cancer-A Systematic Review［J］. Cancers（Basel）， 2023， 15 （6）：1665. doi:10.3390/cancers15061665 doi: 10.3390/cancers15061665
9	QI W， SHI C， ZHANG P， et al. Effect of BRAFV600E mutation detection of fine-needle aspiration biopsy on diagnosis and treatment guidance of papillary thyroid carcinoma［J］. Pathol Res Pract， 2020， 216（8）：153037. doi:10.1016/j.prp.2020.153037 doi: 10.1016/j.prp.2020.153037
10	CHEN H， SONGA， WANG Y， et al. BRAF^V600E mutation test on fine-needle aspiration specimens of thyroid nodules： Clinical correlations for 4600 patients［J］. Cancer Med， 2022， 11（1）：40-49. doi:10.1002/cam4.4419 doi: 10.1002/cam4.4419
11	中国内分泌代谢病专科联盟. 甲状腺结节诊治行业标准［J］. 中华内分泌代谢杂志， 2022， 38（7）：552-554.
12	罗玲玲，夏俊勇，张然，等.分化型甲状腺癌患者¹³¹I治疗后不确定反应的影响因素分析［J］.实用医学杂志， 2021， 37 （20）：2656-2659.
13	赵媛，赵永刚，张春芳，等. 超声、细针穿刺细胞学及BRAF^V600E基因对甲状腺结节的诊断价值［J］. 实用医学杂志， 2020， 36（24）：3420-3424.
14	胡加银，李陶，夏纪筑. C-TIRADS、超声造影、BRAF^V600E基因对TBSRTC Ⅲ类甲状腺结节诊断价值分析［J］. 实用医学杂志， 2022， 38（21）：2739-2744.
15	周斌，翟翼飞，张冬雁，等. 联合BRAFV600E基因检测在甲状腺结节穿刺细胞学诊断为BethesdaⅢ类中的辅助诊断作用［J］. 中华耳鼻咽喉头颈外科杂志， 2020， 55（11）：1057-1062.
16	MAYSON S E， HAUGEN B R. Molecular diagnostic evaluation of thyroid nodules［J］. Endocrinol Metab Clin North Am， 2019， 48（1）：85-97. doi:10.1016/j.ecl.2018.10.004 doi: 10.1016/j.ecl.2018.10.004
17	BROWN A E， LIM K S， CORPUS G， et al. Detection of BRAF mutation in the cytocentrifugation supernatant fluid from fine-needle aspiration of thyroid lesions may enhance the diagnostic yield［J］. Cytojournal， 2017， 14：4. doi:10.4103/1742-6413.200935 doi: 10.4103/1742-6413.200935
18	CABANILLAS M E， RYDER M， JIMENEZ C. Targeted therapy for advanced thyroid cancer： kinase inhibitors and beyond［J］. Endocr Rev， 2019， 40（6）：1573-1604. doi:10.1210/er.2019-00007 doi: 10.1210/er.2019-00007
19	AL-JUNDI M， THAKUR S， GUBBI S， et al. Novel targeted therapies for metastatic thyroid cancer -A Comprehensive Review［J］. Cancers（Basel）， 2020， 12（8）：2104. doi:10.3390/cancers12082104 doi: 10.3390/cancers12082104
20	MACEROLA E， POMA A M， VIGNALI P， et al. Molecular genetics of Follicular-Derived Thyroid Cancer［J］. Cancers（Basel）， 2021， 13（5）：1139. doi:10.3390/cancers13051139 doi: 10.3390/cancers13051139
21	SCHATZ-SIEMERS N， BRANDLER T C， OWEITY T， et al. Hurthle cell lesions on thyroid fine needle aspiration cytology： Molecular and histologic correlation［J］. Diagn Cytopathol， 2019， 47 （10）： 977-985. doi:10.1002/dc.24247 doi: 10.1002/dc.24247
22	HUANG M， YAN C， XIAO J， et al. Relevance and clinicopathologic relationship of BRAF V600E， TERT and NRAS mutations for papillary thyroid carcinoma patients in Northwest China［J］. Diagn Pathol， 2019， 14（1）：74. doi:10.1186/s13000-019-0849-6 doi: 10.1186/s13000-019-0849-6
23	PUZZIELLO A， GUERRA A， MURINO A， et al. Benign thyroid nodules with RAS mutation grow faster［J］. ClinEndocrinol （Oxf）， 2016， 84 （5）：736-740. doi:10.1111/cen.12875 doi: 10.1111/cen.12875
24	叶蕾，李浩榕. 良恶性甲状腺结节的分子鉴别诊断进展［J］. 诊断学理论与实践， 2020， 19（4）：334-338.
25	SONG Y， XU G， MA T， et al. Utility of a multigene testing for preoperative evaluation of indeterminate thyroid nodules： A prospective blinded single center study in China［J］. Cancer Med， 2020， 9（22）：8397-8405. doi:10.1002/cam4.3450 doi: 10.1002/cam4.3450
26	WONG D， YIP S， SORENSEN P H. Methods for Identifying Patients with Tropomyosin Receptor Kinase （TRK） Fusion Cancer［J］. Pathol Oncol Res， 2020， 26（3）：1385-1399. doi:10.1007/s12253-019-00685-2 doi: 10.1007/s12253-019-00685-2
27	LEE Y C， CHEN J Y， HUANG C J， et al. Detection of NTRK1/3 Rearrangements in Papillary Thyroid Carcinoma Using Immunohistochemistry， Fluorescent In Situ Hybridization， and Next-Generation Sequencing［J］. Endocr Pathol， 2020， 31（4）：348-358. doi:10.1007/s12022-020-09648-9 doi: 10.1007/s12022-020-09648-9
28	付莎，李阳阳，郑娜芬，等. NTRK基因融合阳性甲状腺乳头状癌9例临床病理特征［J］. 临床与实验病理学杂志， 2023， 39（12）：1465-1469+1475.
29	ZHAO X， KOTCH C， FOX E， et al. NTRK Fusions Identified in Pediatric Tumors： The Frequency， Fusion Partners， and Clinical Outcome［J］. JCO Precis Oncol， 2021， 1：PO.20.00250. doi:10.1200/po.20.00250 doi: 10.1200/po.20.00250
30	CHU Y H， DIAS-SANTAGATA D， FARAHANI A A， et al. Clinicopathologic and molecular characterization of NTRK-rearranged thyroid carcinoma （NRTC）［J］. Mod Pathol， 2020， 33（11）：2186-2197. doi:10.1038/s41379-020-0574-4 doi: 10.1038/s41379-020-0574-4
31	GRACEFFA G， PATRONE R， VIENI S， et al. Association between Hashimoto's thyroiditis and papillary thyroid carcinoma： a retrospective analysis of 305 patients［J］. BMC EndocrDisord， 2019， 19（）：26. doi:10.1186/s12902-019-0351-x doi: 10.1186/s12902-019-0351-x
32	孙康，汪晓明，王建国. 甲状腺乳头状癌合并桥本甲状腺炎的临床特点［J］. 实用医学杂志， 2023， 39 （13）：1641-1646.

基因	突变位点	例数
合计		52
BRAF	V600E	33
EZH1	Q571R	4
	Q571K	1
	Y642F	1
HRAS	Q61R	2
KRAS	G12D	2
	G12V	1
NRAS	Q61K	1
NTRK3	ETV6-NTRK3	2
RET	CCDC6-RET	1
SPOP	P94R	3
TERT	C228T	1
ZNF148	Q542*	1

项目	性别		年龄		Bethesda分级
项目	男（n = 28）	女（n = 69）	≤ 43岁（n = 34）	> 43岁（n = 63）	Ⅰ级（n = 8）	Ⅱ级（n = 44）	Ⅲ级（n = 9）	Ⅳ级（n = 4）	Ⅴ级（n = 10）	Ⅵ级（n = 22）	合计（n = 97）
BRAF
突变	16	17	19	14	0	3	4	0	7	19	33
未突变	12	52	15	49	8	41	5	4	3	3	64
χ²值	9.375		11.146		54.568
P值	0.002		0.001		< 0.001
EZH1
突变	0	6	1	5	0	6	0	0	0	0	6
未突变	28	63	33	58	8	38	9	4	10	22	91
χ²值	1.313		0.284		4.662
P值	0.252		0.594		0.344
KRAS
突变	0	3	0	3	0	2	1	0	0	0	3
未突变	28	66	34	60	8	42	8	4	10	22	94
χ²值	-		0.460		3.786
P值	0.554		0.498		0.511
HRAS
突变	0	2	1	1	0	2	0	0	0	0	2
未突变	28	67	33	62	8	42	9	4	10	22	95
χ²值	-		-		3.244
P值	1		1		0.792
NRAS
突变	0	1	1	0	0	1	0	0	0	0	1
未突变	28	68	33	63	8	43	9	4	10	22	96
χ²值	-		-		5.051
P值	1		0.351		1

项目	组织学		准确性（%）	χ²值	P值
项目	恶性	良性	准确性（%）	χ²值	P值
细胞学			81.8	-	0.031
阳性	24	0
阴性	6	3
细胞学+NGS			97.0	-	1.000
阳性	30	1
阴性	0	2

临床病理特征	例数	BRAF		χ²值	P值
临床病理特征	例数	突变	未突变	χ²值	P值
性别				-	0.682
男	15	10	5
女	15	12	3
年龄				-	0.092
≤ 43岁	13	12	1
> 43岁	17	10	7
亚型				3.970	0.102
经典型	18	15	3
浸润性滤泡型	7	3	4
高细胞型	5	4	1
伴桥本氏甲状腺炎				-	0.071
是	8	8	0
否	22	14	8
肿块最大径				-	1.000
≤ 1 cm	23	20	3
> 1 cm	7	6	1
淋巴结转移				-	1.000
是	16	12	4
否	14	10	4

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Application of FNA combined with next⁃generation sequencing in the diagnosis and treatment of thyroid nodules

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