Verma T, et al. The role of the ThyGeNEXT oncogene panel used in combination with the expanded miRNA panel ThyraMIRv2 in Indeterminate thyroid nodules: A large, blinded, real-world, observational study. Cancer Cytopathol. 2024;132(9):556-563. doi:10.1002/cncy.22829
An observational study provided data supporting the high performance of the ThyGeNEXT®+ThyraMIR®v2 combination testing platform for evaluating cytologically indeterminate thyroid nodules.1 The performance metrics aligned with the most recent clinical validation study, helping reinforce the utility of this combination approach in everyday clinical settings.1,2
Study Overview
This observational study evaluated 338 consecutive patient samples with cytologically indeterminate thyroid nodules1:
- 258 samples with an atypia of undetermined significance (Bethesda III) cytological diagnosis
- 80 samples with a follicular neoplasm (Bethesda IV) cytological diagnosis
ThyGeNEXT+ThyraMIRv2 testing was performed on all samples.1
Performance Metrics
The performance metrics from the observational study aligned with a previous clinical validation study1-3:
| Test Parameter | Observational Study (14% Prevalence)1* Actual | Observational Study (30% Prevalence)1* Modeled | Clinical Validation Study (30% Prevalence)2,3* |
|---|---|---|---|
| Sensitivity | 96 (86-99) | 96 (86-99) | 98 (90-99) |
| Specificity | 99 (96-99) | 99 (96-99) | 98 (94-99) |
| NPV† | 99% (97-99) | 98% (92-99) | 99% (94-99) |
| PPV† | 89% (74-95) | 95% (88-98) | 94%‡ |
Key Insights
The observational study reported a benign call rate (BCR) of 79.3%, meaning that over 70% of the indeterminate cases were identified as benign (negative) by the molecular test.1,4 The BCR is an important indicator of the overall effectiveness of “rule-out” tests, and high BCRs have been shown to be associated with reduced healthcare costs.1,4
Additionally, there were no false negatives reported over an average 30-month follow-up period.1 The study also reported a very low false-positive rate and a potential reduction in unnecessary surgeries.1
This observational study demonstrated that the ThyGeNEXT+ThyraMIRv2 combination testing platform delivers high performance in the risk stratification of indeterminate thyroid nodules.1 As the test sensitivity, specificity, NPV, and PPV were closely aligned between the studies, the combination testing approach can help improve clinical decision-making and reduce unnecessary surgeries.1,2
FAQs
How does ThyGeNEXT+ThyraMIRv2 help improve risk stratification of indeterminate thyroid nodules?
ThyGeNEXT+ThyraMIRv2 is a unique combination testing platform that utilizes an assessment of the most common mutations associated with all types of thyroid carcinoma and microRNA signatures that provide deep insight into the epigenetic regulation of cancer signaling pathways. The assessment of microRNAs with ThyraMIRv2 enables the testing platform to help rule in malignancy, even in the absence of identified mutations by ThyGeNEXT.2,5 This dual assessment helps provide a complete picture, improving the risk assessment of indeterminate thyroid nodules from a mutational analysis alone.2,5
Which Bethesda classifications are recommended for ThyGeNEXT+ThyraMIRv2 testing?
ThyGeNEXT+ThyraMIRv2 combination testing is particularly valuable for inconclusive or indeterminate thyroid nodules, specifically those with atypia of undetermined significance (Bethesda III) and follicular neoplasm (Bethesda IV) classifications. This molecular testing platform can help further risk-stratify the indeterminate thyroid nodules and help guide decision-making by helping physicians better understand whether or not the thyroid nodule is likely to become cancerous.
How can ThyGeNEXT+ThyraMIRv2 help impact surgical decision-making?
ThyGeNEXT+ThyraMIRv2 can help improve surgical decision-making for indeterminate thyroid nodules by utilizing both mutational analysis and microRNA signatures–helping to reduce surgeries on benign nodules.1-3,5,6 Observational study data support the high performance of ThyGeNEXT+ThyraMIRv2, aligning with the clinical validation study and reinforcing its utility in everyday clinical settings.1,2
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.
*Within the observational study, unresected, molecular test-negative results were assumed to have benign reference diagnoses.1 Within the clinical validation study, negatives were determined to be benign with unanimous consensus histopathology diagnosis.2
†3-Category performance aligned to clinical decision-making in atypia of undetermined significance (Bethesda III) and follicular neoplasm (Bethesda IV) nodules. NPV and PPV are calculated from moderate and positive thresholds, respectively.2,3,5,7
‡The Finkelstein, et al. study was designed to provide a deeper analysis of microRNA expression and evaluated study samples with the inclusion of surgical outcomes, resulting in an NPV of 99% and a PPV of 96%. When aligned to commercial specimen handling and reporting, the NPV and PPV are 99% and 94%, respectively, for atypia of undetermined significance (Bethesda III) and follicular neoplasm (Bethesda IV) thyroid nodules.2,3,7
References: 1. Verma T, et al. Cancer Cytopathol. 2024;132(9):556-563. doi:10.1002/cncy.22829. 2. Finkelstein SD, et al. Thyroid. 2022;32(11):1362-1371. 3. Data on File. Interpace Diagnostics. 4. Ohori NP, et al. Cancer Cytopathol. 2019;127(3):161-168. 5. Lupo MA, et al. Diagn Cytopathol. 2020;48(12):1254-1264. 6. Chowdhury R, et al. Cancers (Basel). 2025;17(7):1156. 7. Ali SZ, et al. Thyroid. 2023;33(9):1039-1044. doi:10.1089/thy.2023.0141.
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