Clinicopathological Implications of the BRAFV600E Mutation in PTC with Concurrent Hashimoto Thyroiditis

Suyeon Park; Hyemi Kwon; Yun Mi Choi; Min Ji Jeon; Tae Yong Kim; Young Kee Shong; Won Bae Kim; Won Gu Kim; Mijin Kim

doi:10.11106/ijt.2016.9.1.29

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Park, Kwon, Choi, Jeon, Kim, Shong, Kim, Kim, and Kim: Clinicopathological Implications of the BRAFV600E Mutation in PTC with Concurrent Hashimoto Thyroiditis

Original Article

Int J Thyroidol 2016;9(1):29-34.

Published online: 20 May 2016

DOI: https://doi.org/10.11106/ijt.2016.9.1.29

Clinicopathological Implications of the BRAF^V600E Mutation in PTC with Concurrent Hashimoto Thyroiditis

Suyeon Park, Hyemi Kwon, Yun Mi Choi, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim, Won Gu Kim, Mijin Kim

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence: Won Gu Kim, MD, PhD, Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: 82-2-3010-5883, Fax: 82-2-3010-6962, E-mail: wongukim@gmail.com

Received 4 August 2015 Revised 22 January 2016 Accepted 11 May 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Objectives

The relationship between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) is still controversial. Some studies suggested that molecular basis of the association between HT and PTC. BRAF^V600E mutation is the most common genetic alteration founded in PTC. This study was to determine a role of BRAF^V600E mutation in PTC with concurrent HT and their association with other clinicopathological factors.

Materials and Methods

We enrolled 452 patients who underwent thyroid surgery between 2009 and 2012 for classical PTC. The status of BRAF^V600E mutation was evaluated by direct sequencing. HT was defined as presence of lymphocytic thyroiditis in pathology or positive serum anti-thyroid peroxidase antibody.

Results

Total 139 patients (30%) with PTC had coexistence HT. HT was significantly associated female (p=0.006), and younger age (p=0.045). BRAF^V600E mutation was confirmed in 264 patients (58%). The frequency of BRAF^V600E mutation was significantly lower in PTC with coexistence HT (48.2%) compared by PTC without HT (62.9%, p=0.004). However, there was no significant difference in clinicopathological feature of PTC according to the presence of HT in patients with BRAF^V600E mutated PTC. BRAF^V600E mutation was less frequent in PTC with coexistence HT.

Conclusion

These findings suggested that HT and BRAF^V600E mutation might be independent factors in development and progression of PTC.

Keywords: Hashimoto thyroiditis, Papillary thyroid carcinoma, BRAF^V600E mutation

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Fig. 1.

Frequency of BRAF ^V600E mutation in classical PTC according to the coexistence of HT.

Table 1.

Clinical and pathological characteristics of patients with PTC according to the co-existence of HT

	Total (n=452)	HT (n=139)	Without HT (n=313)	p value
Age (years)	48.3±10.92	46.59±10.23	49.1±11.14	0.045∗
Gender (male)	92 (20.4%)	17 (12.2%)	75 (24.0%)	0.006∗
Tumor size (cm)	1.03±0.88	0.95±0.63	1.07±0.97	0.82
Multifocality	137 (30.3%)	50 (36.0%)	87 (27.8%)	0.08
Extrathyroidal invasion	248 (54.9%)	75 (54.0%)	173 (55.3%)	0.91
Cervical LN metastasis				0.36
N1a	154 (34.1%)	41 (29.5%)	113 (36.1%)
N1b	48 (10.6%)	15 (10.8%)	33 (10.5%)
pTNM staging				0.29
I & II	252 (55.8%)	83 (59.7%)	169 (54.0%)
III & IV	197 (43.6%)	55 (39.6%)	142 (45.4%)
BRAF ^V600E mutation	264 (58.4%)	67 (48.2%)	197 (62.9%)	0.004∗

HT: Hashimoto thyroiditis, LN: lymph node, PTC: papillary thyroid cancer, pTNM: pathological tumor-node-metastasis

Table 2.

Univariate and multivariate analysis of the clinical and pathological factors associated with co-existence of HT in patients with classical PTC

	Univariate analysis		Multivariate analysis
	OR (95% CI)	p value	OR (95% CI)	p value
Gender (female)	1.16 (1.05–1.29)	0.004	1.16 (1.04–1.28)	0.005∗
Age (years)	0.99 (0.991–0.999)	0.023	0.99 (0.991–0.998)	0.013
BRAF ^V600E mutation	0.87 (0.80–0.95)	0.003	0.86 (1.08–1.89)	0.012∗

CI: confidence interval, HT: Hashimoto thyroiditis, OR: odds ratio, PTC: papillary thyroid cancer

Table 3.

Clinical and pathological characteristics of patients with BRAF ^V600E mutated PTC according to the co-existence of HT

	HT (n=67)	Without HT (n=197)	p value
Age (years)	45.68±9.37	47.9±10.78	0.15
Gender (male)	7 (10.4%)	46 (23.4%)	0.03∗
Tumor size (cm)	1.00±0.71	1.03±0.77	0.67
Multifocality	57 (85.0%)	27 (13.7%)	0.09
Extrathyroidal invasion	38 (56.7%)	121 (61.4%)	0.68
Cervical LN metastasis			0.12
N1a	17 (25.4%)	77 (39.1%)
N1b	10 (14.9%)	23 (11.7%)
pTNM staging			0.15
I & II	43 (64.2%)	105 (53.3%)
III & IV	24 (35.8%)	92 (46.7%)

HT: Hashimoto thyroiditis, LN: lymph node, PTC: papillary thyroid cancer, pTNM: pathological tumor-node-metastasis

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