×
Home Current Archive Editorial board
News Contact
Review paper

The relation between BRAFV600E mutation and clinicopathological characteristics of papillary thyroid cancer

By
Mehmet Celik Orcid logo ,
Mehmet Celik
Contact Mehmet Celik

Department of Endocrinology and Metabolism, School of Medicine, Trakya University, Edirne, Turkey

Buket Yılmaz Bulbul ,
Buket Yılmaz Bulbul

Department of Endocrinology and Metabolism, School of Medicine, Trakya University, Edirne, Turkey

Semra Ayturk ,
Semra Ayturk

Department of Endocrinology and Metabolism, School of Medicine, Trakya University, Edirne, Turkey

Yusuf Durmus ,
Yusuf Durmus

Department of Internal Medicine, School of Medicine, Trakya University, Edirne, Turkey

Hakan Gurkan ,
Hakan Gurkan

Department of Genetic, School of Medicine, Trakya University, Edirne, Turkey

Nuray Can ,
Nuray Can

Department of Pathology, School of Medicine, Trakya University, Edirne, Turkey

Ebru Tastekin ,
Ebru Tastekin

Department of Pathology, School of Medicine, Trakya University, Edirne, Turkey

Funda Ustun ,
Funda Ustun

Department of Nuclear Medicine, School of Medicine, Trakya University, Edirne, Turkey

Atakan Sezer ,
Atakan Sezer

Department of Surgery, School of Medicine, Trakya University, Edirne, Turkey

Sibel Guldiken
Sibel Guldiken

Department of Endocrinology and Metabolism, School of Medicine, Trakya University, Edirne, Turkey

Abstract

Aim
BRAF mutation inhibits many tumour suppressor genes, increases pro-angiogenic molecules and reduces radioactive iodine uptake of tumour in papillary thyroid cancer (PTC), giving it more aggressive clinical characteristics. In this study, we aimed to evaluate the effect of BRAF V600E mutation on the clinicopathological features in patients with PTC.
Methods
The laboratory and clinical findings of 256 PTC patients who were referred to our clinic between 2007 and 2017 were assessed. Subjects involved in the study were divided into two groups depending on the presence of BRAF V600E mutation. Results
BRAF V600E mutation testing gave positive results for 65 (25.4%) out of 256 patients. No significant correlation between BRAF V600E mutation, age and gender was detected. There was no difference between the groups in terms of tumour variant, tumour localization, tumour focality, and perineural invasion. In terms of histopathologic characteristics, presence of tumour capsular invasion (p=0.027), extrathyroidal extension (ETE) (p=0.002), absence of pathologically detected lymphocytic thyroiditis (p=0.006) and radio iodine I-131 treatment (p=0.001) were significantly higher in BRAF V600E (+) patients. During a followup period, four patients with BRAF V600E (+) and two patients with BRAF V600E (-) status underwent lateral neck dissection due to lymph node metastasis (p=0.01).
Conclusion
The presence of BRAF V600E mutation was proved to be a poor prognostic factor. However, in order to further assess the prognostic effect of BRAF V600E mutation in this group of patients and particularly its effect on mortality, long term followup results must be evaluated.

References

1.
Haugen B, Alexander E, Bible K, Doherty G, Mandel S, Nikiforov Y, et al. 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. 2015. p. 1–133.
2.
Sak S. Variants of papillary thyroid carcinoma: multiple faces of a familiar tumor. Turk Patoloji Derg. 2015. p. 34–47.
3.
Pusztaszeri M, Auger M. Update on the cytologic features of papillary thyroid carcinoma variants. Diagn Cytopathol. 2017. p. 714–30.
4.
Pontius L, Oyekunle T, Thomas S, Stang M, Scheri R, Roman S, et al. Projecting survival in papillary thyroid cancer: a comparison of the Seventh and Eighth Editions of the American Joint Commission on Cancer/Union for International Cancer Control Staging Systems in two contemporary national patient cohorts. Thyroid. 2017. p. 1408–16.
5.
Li D, Zhang Y, Xu H, Zhang X. The role of BRAF in the pathogenesis of thyroid carcinoma. Front Biosci (Landmark Ed). 2015. p. 1068–78.
6.
Czarniecka A, Oczko-Wojciechowska M, Barczyński M. BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC) recurrence. Gland Surg. 2016. p. 495–505.
7.
Xing M, Alzahrani A, Carson K, Viola D, Elisei R, Bendlova B, et al. Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer. JAMA. 2013. p. 1493–501.
8.
Sancisi V, Nicoli D, Ragazzi M, Piana S, Ciarrocchi A. BRAFV600E mutation does not mean distant metastasis in thyroid papillary carcinomas. J Clin Endocrinol Metab. 2012. p. 1745–9.
9.
Niederer-Wüst S, Jochum W, Förbs D, Brändle M, Bilz S, Clerici T, et al. Impact of clinical risk scores and BRAF V600E mutation status on outcome in papillary thyroid cancer. Surgery. 2015. p. 119–25.
10.
Ito Y, Yoshida H, Kihara M, Kobayashi K, Miya A, Miyauchi A. BRAF (V600E) mutation analysis in papillary thyroid carcinoma: is it useful for all patients. World J Surg. 2014. p. 679–87.
11.
Elisei R, Viola D, Torregrossa L. The BRAF (V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: single-institution results from a large cohort study. J Clin Endocrinol Metab. 2012. p. 4390–8.
12.
Tang K, Lee C. BRAF mutation in papillary thyroid carcinoma: pathogenic role and clinical implications. J Chin Med Assoc. 2010. p. 113–28.
13.
Huang F, Fang W, Ye L, Zhang X, Shen L, Han R, et al. BRAF mutation correlates with recurrent papillary thyroid carcinoma in Chinese patients. Curr Oncol. 2014. p. 740–7.
14.
Tufano R, Teixeira G, Bishop J, Carson K, Xing M. BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis. Medicine (Baltimore). 2012. p. 274–86.
15.
Yip L, Nikiforova M, Carty S, Yim J, Stang M, Tublin M, et al. Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation. Surgery. 2009. p. 1215–23.
16.
Fugazzola L, Puxeddu E, Avenia N, Romei C, Cirello V, Cavaliere A, et al. Correlation between B-RAFV600E mutation and clinico-pathologic parameters in papillary thyroid carcinoma: data from a multicentric Italian study and review of the literature. Endocr Relat Cancer. 2006. p. 455–64.
17.
Kim S, Lee K, Myong J, Park J, Jeon Y, Min H, et al. BRAF V600E mutation is associated with tumor aggressiveness in papillary thyroid cancer. World J Surg. 2012. p. 310–7.
18.
Kim W, Ha T, Bae S. Clinical implications of the BRAF mutation in papillary thyroid carcinoma and chronic lymphocytic thyroiditis. J Otolaryngol Head Neck Surg. 2018. p. 4.

Citation

Authors retain copyright. This work is licensed under a Creative Commons Attribution 4.0 International License. Creative Commons License

 

Article metrics

Google scholar: See link

The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.