Clinical Utility of BRAF, NRAS, and TERT Promoter Mutation in Preoperative Thyroid Fine-Needle Aspiration Biopsy: A Diagnostic Study From Dharmais Cancer Hospital.

Adhitya Perdana,Rachmawati Rachmawati,Bob Andinata,Rizky Putri,Bayu Brahma

doi:10.31557/apjcp.2020.21.11.3267

Abstract

Objective:Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital. Methods:We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results. Results:Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy. Conclusion:Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.

Highlights

The incidence of thyroid cancer has surged globally in the past three decades, with papillary thyroid carcinoma (PTC) as the most frequent histopathologic subtypes (Bray et al, 2018; Liu et al, 2017; Pellegriti et al, 2013)
The combination of fine-needle aspiration biopsy (FNAB) cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy
Thyroid cancer incidence has been reported to be the top 5 cause of cancer in Indonesia accounting for 4.2% of all new cancer cases among women in 2018 (World Health Organization, 2019)

Summary

Introduction

The incidence of thyroid cancer has surged globally in the past three decades, with papillary thyroid carcinoma (PTC) as the most frequent histopathologic subtypes (Bray et al, 2018; Liu et al, 2017; Pellegriti et al, 2013). Fine needle aspiration biopsy (FNAB) has been broadly accepted as an initial screening test for patients with thyroid nodules. This test has led to a better assessment for patient’s treatment decisions with a high sensitivity rate reported from 65% to 98%, respectively (Gharib and Goellner, 1993; Yang et al, 2007). About 10-40% of cases are diagnosed as indeterminate for malignancy and up to 10% of benign cytology may have a false-negative result (Nikiforov et al, 2009; Yeh et al, 2004) These findings demand improvement for diagnostic accuracy of patients with indeterminate cytology results

Methods

Results

Conclusion