Molecular Diagnosis of Thyroid Nodules Using Next-Generation Sequencing in the Chinese Population

TL;DR

This study uses next-generation sequencing to improve the diagnosis of thyroid nodules in the Chinese population, especially for cases where traditional methods are uncertain.

Contribution

The study introduces a 6-gene test panel that enhances diagnostic accuracy for thyroid nodules with indeterminate fine-needle aspiration results.

Findings

The 6-gene test panel achieved 84.87% sensitivity and 95.15% positive predictive value in diagnosing thyroid nodules.

BRAF V600E mutations were most prevalent (36.32%) among the tested nodules.

The panel showed 86.36% accuracy for Bethesda III, IV, and V nodules.

Abstract

Background: Fine-needle aspiration (FNA) cytology remains a challenge in the diagnosis of indeterminate thyroid nodules. Molecular testing can bridge the gap left by FNA cytology and improve the diagnostic accuracy of FNA.

Methods: 786 FNA samples and 40 formalin-fixed paraffin-embedded (FFPE) specimens from thyroid nodules were enrolled in next-generation sequencing (NGS) molecular testing, which included gene mutation and gene fusion analysis. The molecular diagnostic performance was assessed by analyzing sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value (PPV).

Results: Among 826 thyroid nodules, 409 were NGS-positive (49.52%), with a high prevalence of BRAF V600E (36.32%, 300/826) and RAS (9.32%, 77/826) mutations, a low prevalence of TERT promoter mutations (1.69%, 14/826), and gene fusions involving RET (1.82%, 15/826), NTRK3 (0.73%, 6/826), ALK (0.24%, 2/826), and PAX8-PPARG (0.12%, 1/826). With the analysis of genetic profiles in thyroid nodules, BRAF V600E, TERT mutations, and gene fusions were included in the 6-gene test panel. The overall diagnostic performance of the 6-gene test panel, including sensitivity, specificity, accuracy, NPV, and PPV, was 84.87%, 89.61%, 86.26%, 71.13%, and 95.15%, respectively. For thyroid nodules in Bethesda III, IV, and V, the diagnostic sensitivity, specificity, accuracy, NPV, and PPV of the panel were 85.71%, 88.89%, 86.36%, 61.54%, and 96.77%, respectively.

Conclusion: The results reveal that the 6-gene test panel as a “rule in” test in a clinical setting improves the accuracy of FNA cytology, potentially assisting in the diagnosis of the thyroid nodules with indeterminate FNA cytology.

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