Diagnostic value of BRAF<b><sup>V600E</sup></b> mutation in high-risk thyroid nodules with easily underdiagnosed FNAB results_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 YU Jing , WANG Fengqin , YAO Wenjuan , WU Dongmei , LIU Dapeng

Department of Pathology, Hebei Petrochina Central Hospital, Langfang, Hebei 065000, P. R. China;

Corresponding author：

YU Jing, Email: ygs851113@sina.com

Keywords：

thyroid nodule; BRAF^V600E mutation; fine-needle aspiration biopsy

DOI：

10.7507/1007-9424.201904098

Video：

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Objective To evaluate the diagnostic value of BRAF^V600E mutation test in high-risk thyroid nodules with easily underdiagnosed fine-needle aspiration biopsy (FNAB) results.Methods Retrospectively collected 122 cases of thyroid nodule who treated in the Hebei Petrochina Central Hospital between January 2017 and December 2018, all the cases admitted preoperative ultrasound and FNAB detection. All of the patients had the non-positive cytological results of FNAB and the high-risk features of ultrasound. Contrasted the postoperative pathological coincidence rate of combination of FNAB and BRAF^V600E test with FNAB alone.Results The BRAF^V600E mutation rate was 27.0% (33/122). The positive rate of BRAF^V600E mutation increased with the increase of ultrasound thyroid imaging reporting and data system(TI-RADS) grade (P<0.05), which was independent of patients’ age, gender, number of nodules, diameter of nodules, and FNAB results (P>0.05). The coincidence rate of FNAB combined with BRAF^V600E mutation detection was higher than that of FNAB alone ［86.9% (106/122) vs. 69.7% (85/122), P<0.05).Conclusions The BRAF^V600E mutation test can detect papillary thyroid carcinoma that might be missed by FNAB. We recommend that FNAB should be routinely accompanied by the BRAF^V600E mutation test in the high-risk thyroid nodules.

Citation： YU Jing, WANG Fengqin, YAO Wenjuan, WU Dongmei, LIU Dapeng. Diagnostic value of BRAF^V600E mutation in high-risk thyroid nodules with easily underdiagnosed FNAB results. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(9): 1083-1086. doi: 10.7507/1007-9424.201904098 Copy

1.	Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab, 2009, 94(6): 2092-2098.
2.	何榕洲, 江瑜, 余济春, 等. BRAF 基因与甲状腺癌关系的研究进展. 中华外科杂志, 2016, 54(3): 237-240.
3.	黄侃, 陈政波, 彭林. 甲状腺细针穿刺活检联合 BRAF 基因突变检测的临床意义. 中华普通外科杂志, 2018, 33(9): 783-784.
4.	Koh J, Choi JR, Han KH, et al. Proper indication of BRAF^V600E mutation testing in fine-needle aspirates of thyroid nodules. PLoS One, 2013, 8(5): e64505.
5.	Zhang YZ, Xu T, Cui D, et al. Value of TIRADS, BSRTC and FNA-BRAF^V600E mutation analysis in differentiating high-risk thyroid nodules. Sci Rep, 2015, 5: 16927.
6.	张晓芳, 刘志艳. 2018 版甲状腺细针穿刺活检细胞病理学 Bethesda 报告系统解读. 中华病理学杂志, 2018, 47(9): 729-732.
7.	Gharib H, Papini E, Garber JR, et al. American association of clinical endocrinologists, American college of endocrinology and associazione medici endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules–2016 update. Endocr Pract, 2016, 22(5): 622-639.
8.	Proietti A, Borrelli N, Giannini R, et al. Molecular characterization of 54 cases of false-negative fine-needle aspiration among 1 347 papillary thyroid carcinomas. Cancer Cytopathol, 2014, 122(10): 751-759.
9.	Kim SY, Kim EK, Kwak JY, et al. What to do with thyroid nodules showing benign cytology and BRAF^V600E mutation? A study based on clinical and radiologic features using a highly sensitive analytic method. Surgery, 2015, 157(2): 354-361.
10.	石怀银. BRAF 基因突变及 CK19、Galectin-3、TRβ1、B-raf 蛋白表达在甲状腺乳头状癌病理诊断及预后中的意义. 北京: 中国人民解放军医学院, 2014.
11.	Song JY, Sun SR, Dong F, et al. Predictive value of BRAF^V600E mutation for lymph node metastasis in papillary thyroid cancer: a meta-analysis. Curr Med Sci, 2018, 38(5): 785-797.
12.	Bandoh N, Akahane T, Goto T, et al. Targeted next-generation sequencing of cancer-related genes in thyroid carcinoma: a single institution’s experience. Oncol Lett, 2018, 16(6): 7278-7286.
13.	Park JY, Yi JW, Park CH, et al. Role of BRAF and RAS mutations in extrathyroidal extension in papillary thyroid cancer. Cancer Genomics Proteomics, 2016, 13(2): 171-181.
14.	Zhang H, Chen D. Synergistic inhibition of MEK/ERK and BRAF^V600E with PD98059 and PLX4032 induces sodium/iodide symporter (NIS) expression and radioiodine uptake in BRAF mutated papillary thyroid cancer cells. Thyroid Res, 2018, 11: 13.
15.	Xie H, Wei B, Shen H, et al. BRAF mutation in papillary thyroid carcinoma (PTC) and its association with clinicopathological features and systemic inflammation response index (SIRI). Am J Transl Res, 2018, 10(8): 2726-2736.
16.	Zhou D, Li Z, Bai X. BRAF^V600E and RET/PTC promote the activity of nuclear factor-κB, inflammatory mediators, and lymph node metastasis in papillary thyroid carcinoma: a study of 50 patients in Inner Mongolia. Med Sci Monit, 2018, 24: 6795-6808.
17.	Chernaya G, Mikhno N, Khabalova T, et al. The expression profile of integrin receptors and osteopontin in thyroid malignancies varies depending on the tumor progression rate and presence of BRAF^V600E mutation. Surg Oncol, 2018, 27(4): 702-708.
18.	Chen J, Li XL, Zhao CK, et al. Conventional ultrasound, immunohistochemical factors and BRAF^V600E mutation in predicting central cervical lymph node metastasis of papillary thyroid carcinoma. Ultrasound Med Biol, 2018, 44(11): 2296-2306.
19.	Iva J, Filip G, Martin B, et al. The significance of BRAF^V600E mutation in thyroid cancer in terms of novel targeted therapies–overview of current knowledge and studies. Klin Onkol, 2018, 31(5): 339-344.
20.	Cheng L, Jin Y, Liu M, et al. HER inhibitor promotes BRAF/MEK inhibitor-induced redifferentiation in papillary thyroid cancer harboring BRAF^V600E. Oncotarget, 2017, 8(12): 19843-19854.
21.	Liu C, Chen T, Liu Z. Associations between BRAF^V600E and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Oncol, 2016, 14(1): 241.
22.	Nikiforov YE. Role of molecular markers in thyroid nodule management: then and now. Endocr Pract, 2017, 23(8): 979-988.
23.	Beiša A, Beiša V, Stoškus M, et al. The value of the repeated examination of BRAF^V600E mutation status in diagnostics of papillary thyroid cancer. Endokrynol Pol, 2016, 67(1): 35-40.
24.	Li J, Liu J, Yu X, et al. BRAF^v600e mutation combined with thyroglobulin and fine-needle aspiration in diagnosis of lymph node metastasis of papillary thyroid carcinoma. Pathol Res Pract, 2018, 214(11): 1892-1897.
25.	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. Head Neck, 2016, 38(7): 1017-1021.
26.	Chen X, Zhou Q, Wang F, et al. Value of BRAF^V600E in high-risk thyroid nodules with benign cytology results. AJNR Am J Neuroradiol, 2018, 39(12): 2360-2365.

1. Nikiforov YE, Steward DL, Robinson-Smith TM, et al. Molecular testing for mutations in improving the fine-needle aspiration diagnosis of thyroid nodules. J Clin Endocrinol Metab, 2009, 94(6): 2092-2098.
2. 何榕洲, 江瑜, 余济春, 等. BRAF 基因与甲状腺癌关系的研究进展. 中华外科杂志, 2016, 54(3): 237-240.
3. 黄侃, 陈政波, 彭林. 甲状腺细针穿刺活检联合 BRAF 基因突变检测的临床意义. 中华普通外科杂志, 2018, 33(9): 783-784.
4. Koh J, Choi JR, Han KH, et al. Proper indication of BRAF^V600E mutation testing in fine-needle aspirates of thyroid nodules. PLoS One, 2013, 8(5): e64505.
5. Zhang YZ, Xu T, Cui D, et al. Value of TIRADS, BSRTC and FNA-BRAF^V600E mutation analysis in differentiating high-risk thyroid nodules. Sci Rep, 2015, 5: 16927.
6. 张晓芳, 刘志艳. 2018 版甲状腺细针穿刺活检细胞病理学 Bethesda 报告系统解读. 中华病理学杂志, 2018, 47(9): 729-732.
7. Gharib H, Papini E, Garber JR, et al. American association of clinical endocrinologists, American college of endocrinology and associazione medici endocrinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules–2016 update. Endocr Pract, 2016, 22(5): 622-639.
8. Proietti A, Borrelli N, Giannini R, et al. Molecular characterization of 54 cases of false-negative fine-needle aspiration among 1 347 papillary thyroid carcinomas. Cancer Cytopathol, 2014, 122(10): 751-759.
9. Kim SY, Kim EK, Kwak JY, et al. What to do with thyroid nodules showing benign cytology and BRAF^V600E mutation? A study based on clinical and radiologic features using a highly sensitive analytic method. Surgery, 2015, 157(2): 354-361.
10. 石怀银. BRAF 基因突变及 CK19、Galectin-3、TRβ1、B-raf 蛋白表达在甲状腺乳头状癌病理诊断及预后中的意义. 北京: 中国人民解放军医学院, 2014.
11. Song JY, Sun SR, Dong F, et al. Predictive value of BRAF^V600E mutation for lymph node metastasis in papillary thyroid cancer: a meta-analysis. Curr Med Sci, 2018, 38(5): 785-797.
12. Bandoh N, Akahane T, Goto T, et al. Targeted next-generation sequencing of cancer-related genes in thyroid carcinoma: a single institution’s experience. Oncol Lett, 2018, 16(6): 7278-7286.
13. Park JY, Yi JW, Park CH, et al. Role of BRAF and RAS mutations in extrathyroidal extension in papillary thyroid cancer. Cancer Genomics Proteomics, 2016, 13(2): 171-181.
14. Zhang H, Chen D. Synergistic inhibition of MEK/ERK and BRAF^V600E with PD98059 and PLX4032 induces sodium/iodide symporter (NIS) expression and radioiodine uptake in BRAF mutated papillary thyroid cancer cells. Thyroid Res, 2018, 11: 13.
15. Xie H, Wei B, Shen H, et al. BRAF mutation in papillary thyroid carcinoma (PTC) and its association with clinicopathological features and systemic inflammation response index (SIRI). Am J Transl Res, 2018, 10(8): 2726-2736.
16. Zhou D, Li Z, Bai X. BRAF^V600E and RET/PTC promote the activity of nuclear factor-κB, inflammatory mediators, and lymph node metastasis in papillary thyroid carcinoma: a study of 50 patients in Inner Mongolia. Med Sci Monit, 2018, 24: 6795-6808.
17. Chernaya G, Mikhno N, Khabalova T, et al. The expression profile of integrin receptors and osteopontin in thyroid malignancies varies depending on the tumor progression rate and presence of BRAF^V600E mutation. Surg Oncol, 2018, 27(4): 702-708.
18. Chen J, Li XL, Zhao CK, et al. Conventional ultrasound, immunohistochemical factors and BRAF^V600E mutation in predicting central cervical lymph node metastasis of papillary thyroid carcinoma. Ultrasound Med Biol, 2018, 44(11): 2296-2306.
19. Iva J, Filip G, Martin B, et al. The significance of BRAF^V600E mutation in thyroid cancer in terms of novel targeted therapies–overview of current knowledge and studies. Klin Onkol, 2018, 31(5): 339-344.
20. Cheng L, Jin Y, Liu M, et al. HER inhibitor promotes BRAF/MEK inhibitor-induced redifferentiation in papillary thyroid cancer harboring BRAF^V600E. Oncotarget, 2017, 8(12): 19843-19854.
21. Liu C, Chen T, Liu Z. Associations between BRAF^V600E and prognostic factors and poor outcomes in papillary thyroid carcinoma: a meta-analysis. World J Surg Oncol, 2016, 14(1): 241.
22. Nikiforov YE. Role of molecular markers in thyroid nodule management: then and now. Endocr Pract, 2017, 23(8): 979-988.
23. Beiša A, Beiša V, Stoškus M, et al. The value of the repeated examination of BRAF^V600E mutation status in diagnostics of papillary thyroid cancer. Endokrynol Pol, 2016, 67(1): 35-40.
24. Li J, Liu J, Yu X, et al. BRAF^v600e mutation combined with thyroglobulin and fine-needle aspiration in diagnosis of lymph node metastasis of papillary thyroid carcinoma. Pathol Res Pract, 2018, 214(11): 1892-1897.
25. 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. Head Neck, 2016, 38(7): 1017-1021.
26. Chen X, Zhou Q, Wang F, et al. Value of BRAF^V600E in high-risk thyroid nodules with benign cytology results. AJNR Am J Neuroradiol, 2018, 39(12): 2360-2365.

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Diagnostic value of BRAF^V600E mutation in high-risk thyroid nodules with easily underdiagnosed FNAB results

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Diagnostic value of BRAFV600E mutation in high-risk thyroid nodules with easily underdiagnosed FNAB results

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Diagnostic value of BRAF^V600E mutation in high-risk thyroid nodules with easily underdiagnosed FNAB results