Endocrinol Metab.  2024 Oct;39(5):777-792. 10.3803/EnM.2024.2034.

Small Multi-Gene DNA Panel Can Aid in Reducing the Surgical Resection Rate and Predicting the Malignancy Risk of Thyroid Nodules

• Oh MY
• Choi HM
• Jang J
• Son H
• Park SS
• Song M
• Kim YH
• Cho SW
• Chai YJ
• Chung W
• Park YJ

• KMID: 2560286
• DOI: http://doi.org/10.3803/EnM.2024.2034

Abstract

Background
We explored the utility of a small multi-gene DNA panel for assessing molecular profiles of thyroid nodules and influencing clinical decisions by comparing outcomes between tested and untested nodules.
Methods
Between April 2022 and May 2023, we prospectively performed fine-needle aspiration (FNA) with gene testing via DNA panel of 11 genes (BRAF, RAS [NRAS, HRAS, KRAS], EZH1, DICER1, EIF1AX, PTEN, TP53, PIK3CA, TERT promoter) in 278 consecutive nodules (panel group). Propensity score-matching (1:1) was performed with 475 nodules that consecutively underwent FNA without gene testing between January 2021 and December 2021 (control group).
Results
In the panel group, positive call rate for mutations was 41.7% (BRAF 16.2%, RAS 12.6%, others 11.5%, double mutation 1.4%) for all nodules, and 40.0% (BRAF 4.3%, RAS 19.1%, others 15.7%, double mutation 0.9%) for indeterminate nodules. Benign call rate was 69.8% for all nodules, and 75.7% for indeterminate nodules. In four nodules, additional TP53 (in addition to BRAF or EZH1) or PIK3CA (in addition to BRAF or TERT) mutations were co-detected. Sensitivity, specificity, positive predictive value, and negative predictive value were 80.0%, 53.3%, 88.1%, 38.1% for all nodules, and 78.6%, 45.5%, 64.7%, 62.5% for indeterminate nodules, respectively. Panel group exhibited lower surgical resection rates than the control group for all nodules (27.0% vs. 52.5%, P<0.001), and indeterminate nodules (23.5% vs. 68.2%, P<0.001). Malignancy risk was significantly different between the panel and control groups (81.5% vs. 63.9%, P=0.008) for all nodules.
Conclusion
Our panel aids in managing thyroid nodules by providing information on malignancy risk based on mutations, potentially reducing unnecessary surgery in benign nodules or patients with less aggressive malignancies.

Keyword

Gene panel; Indeterminate nodules; Malignancy risk; Thyroid nodule; Resection rate

Figure

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  Fig. 1. Rate of malignancy of indeterminate (classification III and IV) nodules by Korean Thyroid Imaging Reporting and Data System (KTIRADS) category and mutation characteristics. ROM, risk of malignancy.

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  Fig. 2. Percentage distribution of detected mutations of nodules by Bethesda classfication. EZH1, enhancer of zeste 1 polycomb repressive complex 2 subunit; DICER1, dicer 1, ribonuclease III; EIF1AX, eukaryotic translation initiation factor 1A X-linked; PTEN, phosphatase and tensin homolog.

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