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Lee, Ock, Kim, Kwon, Choi, Kim, and Jung: Diagnostic value of BRAFV600E mutation analysis in fine needle aspiration for evaluation of thyroid nodules
Original Article

Kosin Medical Journal 2018;33(1):1-11.

Published online: 21 January 2018

DOI: https://doi.org/10.7180/kmj.2018.33.1.1

Diagnostic value of BRAFV600E mutation analysis in fine needle aspiration for evaluation of thyroid nodules

Hae Won Lee1, So Young Ock1, Bu Kyoung Kim1, Su Kyoung Kwon1, Young Sik Choi1, Jeong Hoon Kim2, Sang Bong Jung3

1Departments of Internal Medicine, College of Medicine, Kosin University, Busan, Korea

2Department of General Surgery, College of Medicine, Kosin University, Busan, Korea

3Department of Clinical Laboratory Science, Dong-Eui Institute of Technology, Busan, Korea

Corresponding Author: Young Sik Choi, Department of Internal Medicine, College of Medicine, Kosin University, 262, Gamcheon-ro, Seo-gu, Busan 49267, Korea Tel: +82-51-990-6102 Fax: +82-51-248-5686 E-mail: yschoi@kosinmed.or.kr

Received 8 January 201615 March 2016       Accepted 20 April 2016

Copyright © 2018 Kosin University School of Medicine Proceedings

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

Objectives

Ultrasound-guided fine-needle aspiration (FNA) is routinely used in the evaluation of thyroid nodules. However, it has several pitfalls, as has been noted in nondiagnostic and indeterminate cases. This study aims to investigate the value of BRAFV600E mutation co-testing in FNA cytology.

Method

A total of 310 patients underwent BRAFV600E mutation co-testing in FNA cytology on thyroid nodules between June 2013 and June 2014. Of the 310 patients, 69 patients who had undergone a surgery for thyroid nodules were included in this study. The presence of the BRAFV600E mutation was determined by allele-specific polymerase chain reaction amplification of exon 15 of the BRAF gene.

Results

Of 69 cases, 33 (47.8%) were BRAFV600E mutation positive. The BRAFV600E mutation was not significantly associated with high-risk features such as tumor size, lymph node metastasis, and pathological stage. The respective diagnostic performance of FNA (P = 0.02), BRAFV600E mutation (P = 0.03), and ultrasonographic (P = 0.00) findings was statistically significant. The sensitivity, specificity and positive predictive value of FNA was 64.9%, 83.3%, and 94.8%. The sensitivity, specificity and positive predictive value of BRAFV600E mutation was 56.1%, 91.7%, and 96.9% and the US features was 91.2%, 91.7%, and 98.1% respectively. However, sensitivity of FNA with BRAFV600E mutation (77.2%) was lower than FNA with US (92.9%) and combination all together (92.9%).

Conclusion

In this study, we found that US features were the most useful in preoperative differential diagnosis of thyroid nodules. BRAFV600E mutation co-testing in FNA cytology was also useful for diagnosis of thyroid tumors.

Keywords: BRAFV600E mutation, Fine-needle aspiration, Thyroid nodules, Ultrasound features

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Table 1.
Fine-needle aspiration, BARFV600E, and final pathologic diagnosis with operation in thyroid nodules
FNA result BRAFV600E mutation Numbers Pathology (n = 69)
Nondiagnostic (n = 3) Negative 3 PTC (n = 3)
Positive 0 None
Benign (n = 17) Negative 14 NH (n = 3), FA (n = 3), FC (n = 2), FVPTC (n = 1), PTC (n = 5)
Positive 3 FA (n = 1), PTC (n = 2)
AUS (n = 7) Negative 3 HT (n = 1), PTC (n = 2)
Positive 4 PTC (n = 4)
Suspicious for FN (n = 3) Negative 2 NH (n = 1), FA (n = 1)
Positive 1 FC (n = 1)
Suspicious for PTC (n = 7) Negative 4 NH (n = 1), HT (n = 1), PTC (n = 2)
Positive 3 PTC (n = 3)
PTC (n = 32) Negative 10 PTC (n = 10)
Positive 22 PTC (n = 22)

FAN, fine needle aspiration; AUS, atypia undetermined significance; FN, follicular neoplasm; PTC, papillary thyroid carcinoma; NH, nodular hyperplasia; FA, follicular adenoma; HT, Hashimoto’s thyroiditis; FC, follicular carcinoma; FVPTC, follicular variant papillary thyroid carcinoma

Table 2.
Correlation between BRAFV600E mutation and various clinicopathological parameters in papillary thyroid carcinomas
Mutation of BRAFV600E, n (%)
 X2 P-value
Wild (n = 23) Mutant (n = 31)
Age
< 45 years 9 (39.1) 12 (38.7) 0.001 0.59
≥ 45 years 14 (60.9) 19 (61.3)
Gender
Male 5 (21.7) 5 (16.1) 0.275 0.42
Female 18 (78.3) 26 (83.9)
Tumor size
≤ 10 ㎜ 21 (91.3) 24 (77.4) 1.833 0.16
> 10 ㎜ 2 (8.7) 7 (22.6)
Calcification
No 15 (65.2) 12 (38.7) 3.711 0.04
Yes 8 (34.8) 19 (61.3)
ETE
No 14 (60.9) 15 (48.4) 0.827 0.26
Yes 9 (39.1) 16 (51.6)
Lymphocytic thyroiditis
No 17 (73.9) 24 (77.4) 0.089 0.50
Yes 6 (26.1) 7 (22.6)
Nodal metastasis
Negative (N0) 19 (82.6) 19 (61.3) 2.878 0.08
Positive (N1a + N1b) 4 (17.4) 12 (38.7)
pTMN staging
I + II 20 (87.0) 25 (80.6) 0.379 0.40
III + IV 3 (13.0) 6 (19.4)

ETE; extrathyroidal extension. According to the TNM staging system: N1a indicates lymph node metastasis to level VI (pretracheal, tracheal and prelaryngeal nodes); N1b indicates metastasis to unilateral, bilateral, contralateral cervical or superior mediastinal nodes. Calculated by the χ2-test and Fisher’s exact test

Table 3.
Sensitivity, specificity, positive predictive value and negative predictive value according to diagnostic modalities
Sensitivity % Specificity % PPV % NPV % P-value
Cytology 64.9 (37/57) 83.3 (10/12) 94.8 (37/39) 66.7 (20/30) 0.02
BRAFV600E 56.1 (32/57) 91.7 (11/12) 96.9 (32/33) 30.1 (11/36) 0.03
US assessment 91.2 (52/57) 91.7 (11/12) 98.1 (52/53) 68.8 (11/16) 0.00
Cytology with BRAFV600E 77.2 (44/57) 75.0 (9/12) 93.6 (44/47) 40.9 (9/22) 0.00
Cytology with US 92.9 (53/57) 83.3 (10/12) 96.3 (53/55) 71.4 (10/14) 0.00
All combination 92.9 (53/57) 75.0 (9/12) 94.6 (53/56) 69.2 (9/13) 0.00

PPV; positive predictable value, NPV; negative predictable value

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