Association between BRAF<b><sup>V600E</sup></b> gene mutation and extrathyroidal extension in papillary thyroid carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHAN Ling ,  SUN Shengrong

Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;

Corresponding author：

SUN Shengrong, Email: sun137@sina.com

Keywords：

BRAF^V600E gene mutation; papillary thyroid carcinoma; extrathyroidal extension

DOI：

10.7507/1007-9424.202012131

Video：

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Objective To investigate association between BRAF^V600E gene mutation and extrathyroidal extension (ETE) among patients with papillary thyroid carcinoma (PTC).Methods A retrospective study was conducted to collect all PTC surgical patients in the Renmin Hospital of Wuhan University from 2017 to 2019. The patients tested for BRAF^V600E gene mutation were selected, and the association between BRAF^V600E gene mutation and ETE were analyzed.Results The BRAF^V600E gene mutation test was performed only in 273 cases, 223 and 50 of whom were BRAF^V600E gene with and without mutation, respectively; 194 and 79 of whom had ETE and no ETE, respectively. Univariate analysis showed that the incidence rate with BRAF^V600E gene mutation was higher in the patients with ETE as compared with the patients without ETE (86.1% vs 70.9%, P=0.003) and the incidence rate of ETE was higher in the patients with BRAF^V600E gene mutaton than in the patients without BRAF^V600E gene mutaton (74.9% vs 54.0%, P=0.003). In addition, the incidence rates of ETE in the patients with tumor diameter >1 cm, bilaterality, and multifocality were higher than those in the patients with tumor diameter ≤1 cm (86.7% vs 61.3%, P<0.001), unilaterality (89.6% vs 63.8%, P<0.001), and single lesion (85.7% vs 60.9%, P<0.001), respectively. The incidence rate of ETE was increased with the increase of lymph node stage (P=0.003). Multivariate logistic regression analysis showed tumor size >1 cm [OR=3.606, 95%CI (1.758, 7.396), P<0.001], multifocality [OR=2.524, 95%CI (1.154, 5.519), P=0.020], with BRAF^V600E gene mutaton [OR=3.022, 95%CI (1.443, 6.326), P=0.003] were the risk factors for ETE.Conclusion The preliminary results of this study suggest that PTC patients with BRAF^V600E gene mutaton are more likely to gross ETE.

Citation： ZHAN Ling, SUN Shengrong. Association between BRAF^V600E gene mutation and extrathyroidal extension in papillary thyroid carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(9): 1159-1164. doi: 10.7507/1007-9424.202012131 Copy

1.	Zhao L, Pang P, Zang L, et al. Features and trends of thyroid cancer in patients with thyroidectomies in Beijing, China between 1994 and 2015: a retrospective study. BMJ Open, 2019, 9(1): e023334.
2.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021 Feb 4. doi: 10.3322/caac.21660. Online ahead of print.
3.	Zhang J, Cheng X, Shen L, et al. The association between lymph node stage and clinical prognosis in thyroid cancer. Front Endocrinol (Lausanne), 2020, 11: 90.
4.	黄璐, 李超, 王薇, 等. 甲状腺癌腺外侵犯的意义及最新研究进展. 中华耳鼻咽喉头颈外科杂志, 2019, 54(9): 717-720.
5.	中华人民共和国国家卫生健康委员会. 甲状腺癌诊疗规范(2018年版). 中华普通外科学文献(电子版), 2019, 13(1): 1-15.
6.	Kim KJ, Kim SG, Tan J, et al. BRAF^V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma. Eur J Cancer, 2020, 124: 161-169.
7.	Huang Y, Qu S, Zhu G, et al. BRAF^V600E mutation-assisted risk stratification of solitary intrathyroidal papillary thyroid cancer for precision treatment. J Natl Cancer Inst, 2018, 110(4): 362-370.
8.	Cabanillas ME, Ryder M, Jimenez C. Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond. Endocr Rev, 2019, 40(6): 1573-1604.
9.	McLeod DSA, Zhang L, Durante C, et al. Contemporary debates in adult papillary thyroid cancer management. Endocr Rev, 2019, 40(6): 1481-1499.
10.	宋创业, 严丽, 孟艳林, 等. BRAF^V600E突变在cN0期PTMC颈中央区淋巴结转移中的预测价值. 中华普外科手术学杂志(电子版), 2020, 14(6): 631-634.
11.	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. JAMA Otolaryngol Head Neck Surg, 2013, 139(11): 1164-1170.
12.	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. Thyroid, 2016, 26(1): 1-133.
13.	Amin MB, Edge S, Greene F, et al. AJCC Cancer Staging Manual. 8th edn. New York, NY: Springer International Publishing, 2017.
14.	Sugino K, Nagahama M, Kitagawa W, et al. Risk stratification of pediatric patients with differentiated thyroid cancer: is total thyroidectomy necessary for patients at any risk? Thyroid, 2020, 30(4): 548-556.
15.	宋韫韬, 于文斌, 魏炜, 等. 甲状腺乳头状癌腺外侵犯相关因素分析. 中国实用外科杂志, 2017, 37(11): 1272-1275.
16.	Li G, Li R, Song L, et al. Implications of extrathyroidal extension invading only the strap muscles in papillary thyroid carcinomas. Thyroid, 2020, 30(1): 57-64.
17.	崔文霞, 朱有志, 郑珂, 等. 甲状腺乳头状癌BRAF^V600E基因突变与蛋白表达的临床研究. 中华实验外科杂志, 2018, 35(3): 522-524.
18.	Lim JY, Hong SW, Lee YS, et al. Clinicopathologic implications of the BRAF^V600E mutation in papillary thyroid cancer: a subgroup analysis of 3 130 cases in a single center. Thyroid, 2013, 23(11): 1423-1430.
19.	Yan C, Huang M, Li X, et al. Relationship between BRAF^V600E and clinical features in papillary thyroid carcinoma. Endocr Connect, 2019, 8(7): 988-996.
20.	王越, 赵文娟. 桥本氏甲状腺炎合并PTC临床病理特征与BRAF^V600E基因突变的相关性研究, 青岛大学, 2019.
21.	Kim WW, Ha TK, Bae SK. Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis. J Otolaryngol Head Neck Surg, 2018, 47(1): 4.
22.	Kim SK, Woo JW, Lee JH, et al. Chronic lymphocytic thyroiditis and BRAF^V600E in papillary thyroid carcinoma. Endocr Relat Cancer, 2016, 23(1): 27-34.
23.	Molnár C, Molnár S, Bedekovics J, et al. Thyroid carcinoma coexisting with Hashimoto’s thyreoiditis: clinicopathological and molecular characteristics clue up pathogenesis. Pathol Oncol Res, 2019, 25(3): 1191-1197.
24.	Pessôa-Pereira D, Medeiros MFDS, Lima VMS, et al. Association between BRAF^V600E mutation and clinicopathological features of papillary thyroid carcinoma: a Brazilian single-centre case series. Arch Endocrinol Metab, 2019, 63(2): 97-106.
25.	Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: A review. JAMA, 2019, 322(2): 153-160.
26.	Vita R, Ieni A, Tuccari G, et al. The increasing prevalence of chronic lymphocytic thyroiditis in papillary microcarcinoma. Rev Endocr Metab Disord, 2018, 19(4): 301-309.
27.	Marotta V, Sciammarella C, Chiofalo MG, et al. Hashimoto’s thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer. Endocr Relat Cancer, 2017, 24(9): 485-493.
28.	张艳, 王文栋, 兰霞斌, 等. 甲状腺乳头状癌伴发桥本甲状腺炎的临床研究. 中国癌症杂志, 2019, 29(12): 948-954.
29.	税春燕, 李超, 覃纲, 等. 甲状腺乳头状癌临床病理特征对颈部淋巴结转移风险预测. 中华肿瘤防治杂志, 2019, 26(13): 952-958.
30.	Jain NK, Mostoufi-Moab S, Hawkes CP, et al. Extrathyroidal extension is an important predictor of regional lymph node metastasis in pediatric differentiated thyroid cancer. Thyroid, 2020, 30(7): 1037-1043.
31.	Mazzaferri EL, Kloos RT. Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab, 2001, 86(4): 1447-1463.
32.	Sulaieva O, Chernenko O, Chereshneva Y, et al. Thyroid stimulating hormone levels and BRAF^V600E mutation contribute to pathophysiology of papillary thyroid carcinoma: Relation to outcomes? Pathophysiology, 2019, 26(2): 129-135.

1. Zhao L, Pang P, Zang L, et al. Features and trends of thyroid cancer in patients with thyroidectomies in Beijing, China between 1994 and 2015: a retrospective study. BMJ Open, 2019, 9(1): e023334.
2. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021 Feb 4. doi: 10.3322/caac.21660. Online ahead of print.
3. Zhang J, Cheng X, Shen L, et al. The association between lymph node stage and clinical prognosis in thyroid cancer. Front Endocrinol (Lausanne), 2020, 11: 90.
4. 黄璐, 李超, 王薇, 等. 甲状腺癌腺外侵犯的意义及最新研究进展. 中华耳鼻咽喉头颈外科杂志, 2019, 54(9): 717-720.
5. 中华人民共和国国家卫生健康委员会. 甲状腺癌诊疗规范(2018年版). 中华普通外科学文献(电子版), 2019, 13(1): 1-15.
6. Kim KJ, Kim SG, Tan J, et al. BRAF^V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma. Eur J Cancer, 2020, 124: 161-169.
7. Huang Y, Qu S, Zhu G, et al. BRAF^V600E mutation-assisted risk stratification of solitary intrathyroidal papillary thyroid cancer for precision treatment. J Natl Cancer Inst, 2018, 110(4): 362-370.
8. Cabanillas ME, Ryder M, Jimenez C. Targeted therapy for advanced thyroid cancer: kinase inhibitors and beyond. Endocr Rev, 2019, 40(6): 1573-1604.
9. McLeod DSA, Zhang L, Durante C, et al. Contemporary debates in adult papillary thyroid cancer management. Endocr Rev, 2019, 40(6): 1481-1499.
10. 宋创业, 严丽, 孟艳林, 等. BRAF^V600E突变在cN0期PTMC颈中央区淋巴结转移中的预测价值. 中华普外科手术学杂志(电子版), 2020, 14(6): 631-634.
11. 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. JAMA Otolaryngol Head Neck Surg, 2013, 139(11): 1164-1170.
12. 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. Thyroid, 2016, 26(1): 1-133.
13. Amin MB, Edge S, Greene F, et al. AJCC Cancer Staging Manual. 8th edn. New York, NY: Springer International Publishing, 2017.
14. Sugino K, Nagahama M, Kitagawa W, et al. Risk stratification of pediatric patients with differentiated thyroid cancer: is total thyroidectomy necessary for patients at any risk? Thyroid, 2020, 30(4): 548-556.
15. 宋韫韬, 于文斌, 魏炜, 等. 甲状腺乳头状癌腺外侵犯相关因素分析. 中国实用外科杂志, 2017, 37(11): 1272-1275.
16. Li G, Li R, Song L, et al. Implications of extrathyroidal extension invading only the strap muscles in papillary thyroid carcinomas. Thyroid, 2020, 30(1): 57-64.
17. 崔文霞, 朱有志, 郑珂, 等. 甲状腺乳头状癌BRAF^V600E基因突变与蛋白表达的临床研究. 中华实验外科杂志, 2018, 35(3): 522-524.
18. Lim JY, Hong SW, Lee YS, et al. Clinicopathologic implications of the BRAF^V600E mutation in papillary thyroid cancer: a subgroup analysis of 3 130 cases in a single center. Thyroid, 2013, 23(11): 1423-1430.
19. Yan C, Huang M, Li X, et al. Relationship between BRAF^V600E and clinical features in papillary thyroid carcinoma. Endocr Connect, 2019, 8(7): 988-996.
20. 王越, 赵文娟. 桥本氏甲状腺炎合并PTC临床病理特征与BRAF^V600E基因突变的相关性研究, 青岛大学, 2019.
21. Kim WW, Ha TK, Bae SK. Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis. J Otolaryngol Head Neck Surg, 2018, 47(1): 4.
22. Kim SK, Woo JW, Lee JH, et al. Chronic lymphocytic thyroiditis and BRAF^V600E in papillary thyroid carcinoma. Endocr Relat Cancer, 2016, 23(1): 27-34.
23. Molnár C, Molnár S, Bedekovics J, et al. Thyroid carcinoma coexisting with Hashimoto’s thyreoiditis: clinicopathological and molecular characteristics clue up pathogenesis. Pathol Oncol Res, 2019, 25(3): 1191-1197.
24. Pessôa-Pereira D, Medeiros MFDS, Lima VMS, et al. Association between BRAF^V600E mutation and clinicopathological features of papillary thyroid carcinoma: a Brazilian single-centre case series. Arch Endocrinol Metab, 2019, 63(2): 97-106.
25. Biondi B, Cappola AR, Cooper DS. Subclinical hypothyroidism: A review. JAMA, 2019, 322(2): 153-160.
26. Vita R, Ieni A, Tuccari G, et al. The increasing prevalence of chronic lymphocytic thyroiditis in papillary microcarcinoma. Rev Endocr Metab Disord, 2018, 19(4): 301-309.
27. Marotta V, Sciammarella C, Chiofalo MG, et al. Hashimoto’s thyroiditis predicts outcome in intrathyroidal papillary thyroid cancer. Endocr Relat Cancer, 2017, 24(9): 485-493.
28. 张艳, 王文栋, 兰霞斌, 等. 甲状腺乳头状癌伴发桥本甲状腺炎的临床研究. 中国癌症杂志, 2019, 29(12): 948-954.
29. 税春燕, 李超, 覃纲, 等. 甲状腺乳头状癌临床病理特征对颈部淋巴结转移风险预测. 中华肿瘤防治杂志, 2019, 26(13): 952-958.
30. Jain NK, Mostoufi-Moab S, Hawkes CP, et al. Extrathyroidal extension is an important predictor of regional lymph node metastasis in pediatric differentiated thyroid cancer. Thyroid, 2020, 30(7): 1037-1043.
31. Mazzaferri EL, Kloos RT. Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab, 2001, 86(4): 1447-1463.
32. Sulaieva O, Chernenko O, Chereshneva Y, et al. Thyroid stimulating hormone levels and BRAF^V600E mutation contribute to pathophysiology of papillary thyroid carcinoma: Relation to outcomes? Pathophysiology, 2019, 26(2): 129-135.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Association between BRAF^V600E gene mutation and extrathyroidal extension in papillary thyroid carcinoma

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Association between BRAFV600E gene mutation and extrathyroidal extension in papillary thyroid carcinoma

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Association between BRAF^V600E gene mutation and extrathyroidal extension in papillary thyroid carcinoma