At the 2025 Annual Meeting of the American Thyroid Association® (ATA), poster #477 presented findings from a retrospective analysis of 28,144 indeterminate thyroid nodules classified as Atypia of Undetermined Significance (B-III) and Follicular Neoplasm (B-IV). These samples, collected between September 2022 and April 2025, were evaluated using the combined ThyGeNEXT®+ThyraMIR®v2 molecular testing platform.1
Thyroid nodules classified as B-III or B-IV present a great challenge due to their broad and uncertain risk of malignancy, which can complicate clinical decision-making.1,2 As a result, patients may undergo molecular testing, active surveillance, or surgery depending on the risk assessment.
The ThyGeNEXT+ThyraMIRv2 testing approach combines mutational analysis with microRNA (miRNA) markers. microRNAs are noncoding RNA molecules that play an important role in thyroid cancer, acting as both tumor suppressors and promoters.3,4 Importantly, microRNAs can help rule in malignancy even in the absence of identified mutations.5,6
This retrospective analysis aimed to evaluate how microRNA expression profiling, when combined with mutational analysis, can help improve the risk of malignancy assessment in B-III/B-IV thyroid nodules.1
Key Findings
- The ThyGeNEXT panel identified1:
- BRAF V600E-like mutations in 4.4% of samples
- RAS-like mutations in 18.9% of samples
- 76.7% of nodules were mutation-negative
- The high benign call rate (BCR) was 76.7%, similar to previously reported findings1,3,5,7
- NRAS mutations had the highest prevalence in both B-III (39.9%) and B-IV (34.2%) nodules1
- The ThyraMIRv2 panel further stratified malignancy risk amongst RAS-like mutations and mutation-negative samples using microRNA expression profiling1
- In mutation-negative nodules, 93.2% were classified as low risk, 4.5% as moderate risk, and 2.3% as high risk
- In nodules with RAS-like mutations, 80.2% were classified as low risk, 13.7% as moderate risk, and 6.1% as high risk
The ThyGeNEXT mutational analysis helped identify key oncogene drivers, while the ThyraMIRv2 microRNA profiling helped further risk-stratify within RAS-like mutations and mutation-negative samples.1 Additionally, microRNA profiling can help differentiate thyroid cancer subtypes such as PTC and MTC.4,5
These findings demonstrate that combining mutational and microRNA analysis can help refine malignancy risk assessment in B-III /B-IV thyroid nodules.1 This combination approach may help reduce unnecessary surgeries by defining risk of malignancy within narrow ranges.5,8
The ThyGeNEXT+ThyraMIRv2 combination testing platform can help support more informed clinical decision-making, helping clinicians determine which indeterminate thyroid nodules may benefit from surgery versus surveillance.1
Patient management decisions are based on the independent medical judgment of the physician and molecular test results should be taken into consideration in conjunction with all relevant imaging, clinical findings, patient and family history, as well as patient preference.
References: 1. Timmaraju VA, et al. Refined Risk Stratification of Bethesda III/IV Thyroid Nodules Using ThyGeNEXT®+ThyraMIR®v2. Poster presented at: The American Thyroid Association Annual Meeting; September 13, 2025; Scottsdale, AZ. 2. Alyusuf EY, et al. Front Endocrinol (Lausanne). 2024;15:1326134. 3. Marini F, et al. J Thyroid Res. 2011;(1):407123. 4. Ghafouri-Fard S. Non-coding RNA Research. 2020;5(3):88-98. 5. Finkelstein SD, et. al. Thyroid. 2022;32(11):1362‐1371. 6. Lupo MA, et al. Diagn Cytopathol. 2020;48(12):1254-1264. 7. Verma T, et al. Cancer Cytopathol. 2024;132(9):556-563. 8. Banizs AB, et al. Diagn Cytopathol. 2019;47(4):268-274.
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