J Endocr Surg.  2017 Dec;17(4):175-183. 10.16956/jes.2017.17.4.175.

The Clinical Significance of the BRAF Mutation in Patients with Papillary Thyroid Cancer

Affiliations
  • 1Department of Surgery, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea. servent-lee@hanmail.net

Abstract

PURPOSE
Papillary thyroid cancer (PTC) is the most frequent subtype among thyroid cancers. B-type Raf kinase (BRAF) mutation can be found in approximately 80% of patients with PTC in Korea. However, there is ongoing debate whether BRAF mutation is clinically significant or not in PTC. Therefore, we investigated the clinical significance of BRAF mutation.
METHODS
We retrospectively enrolled 1,503 PTC patients (1,170 who were BRAF positive) among the registered from January in 2009 to October in 2013. The mean follow-up period was 53.0 months (max 173 months). BRAF mutation analysis was performed by restriction fragment length polymorphism-polymerase chain reaction.
RESULTS
In the group with the BRAF mutation, male gender (P=0.003), the capsular invasion (P<0.001), and N1 stage (P<0.001) were more frequent features and there were more central lymph node metastases than in those without the mutation. The frequencies of total thyroidectomy and radioactive iodine (RAI) therapy were not different between the 2 groups (P=0.753 and P=0.139, respectively) and the BRAF mutation was not a prognostic factor for recurrence (P=0.823). The significant prognostic factor for recurrence was the post-RAI therapy stimulated thyroglobulin, only which reflected the response of treatment. It did not differ between the 2 groups in this study.
CONCLUSION
Although the BRAF mutation was not a prognostic factor for the recurrence, but was correlated with the aggressive behavior in this study. Therefore, to determine whether the early surgical treatment is possible in this group is important and it may be a useful preoperative modulator to determine whether early surgical treatment is necessary or not.

Keyword

Papillary carcinoma; Proto-oncogene proteins B-raf; Thyroid neoplasms

MeSH Terms

Carcinoma, Papillary
Follow-Up Studies
Humans
Iodine
Korea
Lymph Nodes
Male
Neoplasm Metastasis
Phosphotransferases
Proto-Oncogene Proteins B-raf
Recurrence
Retrospective Studies
Thyroglobulin
Thyroid Gland*
Thyroid Neoplasms*
Thyroidectomy
Iodine
Phosphotransferases
Proto-Oncogene Proteins B-raf
Thyroglobulin

Figure

  • Fig. 1 Recurrence-free rate was not different between the groups with and without the BRAF mutation. BRAF = B-type Raf kinase.


Reference

1. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA. 2006; 295:2164–2167.
Article
2. Tang KT, Lee CH. BRAF mutation in papillary thyroid carcinoma: pathogenic role and clinical implications. J Chin Med Assoc. 2010; 73:113–128.
Article
3. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid. 2003; 13:381–387.
Article
4. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, 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; 26:1–133.
Article
5. Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocr Rev. 2007; 28:742–762.
Article
6. Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer. 2007; 110:38–46.
Article
7. Riesco-Eizaguirre G, Gutiérrez-Martínez P, García-Cabezas MA, Nistal M, Santisteban P. The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane. Endocr Relat Cancer. 2006; 13:257–269.
Article
8. Elisei R, Ugolini C, Viola D, Lupi C, Biagini A, Giannini R, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab. 2008; 93:3943–3949.
Article
9. Brzeziańska E, Pastuszak-Lewandoska D, Wojciechowska K, Migdalska-Sek M, Cyniak-Magierska A, Nawrot E, et al. Investigation of V600E BRAF mutation in papillary thyroid carcinoma in the Polish population. Neuroendocrinol Lett. 2007; 28:351–359.
10. Fugazzola L, Mannavola D, Cirello V, Vannucchi G, Muzza M, Vicentini L, et al. BRAF mutations in an Italian cohort of thyroid cancers. Clin Endocrinol (Oxf). 2004; 61:239–243.
Article
11. Kim TY, Kim WB, Song JY, Rhee YS, Gong G, Cho YM, et al. The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma. Clin Endocrinol (Oxf). 2005; 63:588–593.
Article
12. Hayashida N, Namba H, Kumagai A, Hayashi T, Ohtsuru A, Ito M, et al. A rapid and simple detection method for the BRAF(T1796A) mutation in fine-needle aspirated thyroid carcinoma cells. Thyroid. 2004; 14:910–915.
Article
13. Knauf JA, Ma X, Smith EP, Zhang L, Mitsutake N, Liao XH, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005; 65:4238–4245.
Article
14. Kim TY, Kim WB, Rhee YS, Song JY, Kim JM, Gong G, et al. The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2006; 65:364–368.
Article
15. Li C, Lee KC, Schneider EB, Zeiger MA. BRAF V600E mutation and its association with clinicopathological features of papillary thyroid cancer: a meta-analysis. J Clin Endocrinol Metab. 2012; 97:4559–4570.
Article
16. Fernandez IJ, Piccin O, Sciascia S, Cavicchi O, Repaci A, Vicennati V, et al. Clinical significance of BRAF mutation in thyroid papillary cancer. Otolaryngol Head Neck Surg. 2013; 148:919–925.
Article
17. Ciappuccini R, Hardouin J, Heutte N, Vaur D, Quak E, Rame JP, et al. Stimulated thyroglobulin level at ablation in differentiated thyroid cancer: the impact of treatment preparation modalities and tumor burden. Eur J Endocrinol. 2014; 171:247–252.
Article
18. Ito Y, Miyauchi A, Inoue H, Fukushima M, Kihara M, Higashiyama T, et al. An observational trial for papillary thyroid microcarcinoma in Japanese patients. World J Surg. 2010; 34:28–35.
Article
19. Sugitani I, Toda K, Yamada K, Yamamoto N, Ikenaga M, Fujimoto Y. Three distinctly different kinds of papillary thyroid microcarcinoma should be recognized: our treatment strategies and outcomes. World J Surg. 2010; 34:1222–1231.
Article
20. Niemeier LA, Kuffner Akatsu H, Song C, Carty SE, Hodak SP, Yip L, et al. A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma. Cancer. 2012; 118:2069–2077.
Article
21. Lin KL, Wang OC, Zhang XH, Dai XX, Hu XQ, Qu JM. The BRAF mutation is predictive of aggressive clinicopathological characteristics in papillary thyroid microcarcinoma. Ann Surg Oncol. 2010; 17:3294–3300.
Article
22. Zheng X, Wei S, Han Y, Li Y, Yu Y, Yun X, et al. Papillary microcarcinoma of the thyroid: clinical characteristics and BRAF(V600E) mutational status of 977 cases. Ann Surg Oncol. 2013; 20:2266–2273.
Article
23. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol. 2010; 321:86–93.
Article
Full Text Links
  • JES
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr