Combination Testing
Go beyond mutational analysis with microRNA pairwise expression profiling
ThyGeNEXT® + ThyraMIR®v2 is the only testing platform that utilizes both mutational and microRNA markers1,2
Expression of thyroid neoplasia involves the combination of mutational and cellular-level (epigenomic) factors2
- Mutations can change protein function which impacts cellular growth and behavior6
- Cellular-level growth regulation includes differential microRNA expression which controls protein translation2
microRNA regulates protein synthesis—providing a view into the cellular biology of pathological conditions7
Differential Pairwise Expression of Suppressor and Promotor microRNAs Yield Unique Profiles2
Benign/Malignant Profile2
- Improves classification of non-mutated samples, RAS-like mutations, and Hürthle cell change
- Effective in both benign and malignant histopathologic subtypes
Strong-Driver Profile8
- Independently confirms the presence of BRAF V600E and/or TERT promoter strong driver mutations
MTC Profile9
- Pairwise microRNA expression is also fully validated for the detection of Medullary Thyroid Cancer
- Particularly helpful in the absence of a mutation
ThyGeNEXT® is a Strategically Designed Mutation Panel
| DNA mutation panel1 | RNA panel1 (# fusions) | ALK* | ALK (2)* |
|---|---|
| BRAF* | BRAF (3)* |
| GNAS | NTRK (8)* |
| HRAS | PPARg (5) |
| KRAS | RET (14)* |
| NRAS | THADA (5) |
| PIK3CA | mRNA markers: NKX2-1, PAX8, TBP, USP33 |
| PTEN | |
| RET* | |
| TERT |
- Worrisome and coexisting mutations are identified, including those that provide therapeutic insight2,11,12
- Both TERT promoter and ALK mutations can reliably help to predict aggressive biological features of thyroid cancer13,14,15
ThyGeNEXT + ThyraMIRv2 Testing Algorithm*1,2,18
*Testing algorithm based upon Bethesda Diagnostic Categories III (AUS/FLUS) and IV (FN/SFN).
ThyGeNEXT samples that are positive for BRAF, TERT, and RET/PTC will solely receive a ThyGeNEXT report. ThyGeNEXT samples that do not result with a mutation or that test positive for markers that have a lower risk of malignancy, such as RAS, will also receive a ThyraMIRv2 report.
NCCN guidelines for management of nodules with B3 and B4 cytology diagnoses include consideration of molecular analysis.19
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. Lupo MA, et al. Diagn Cytopathol. 2020;1-11. https://doi.org/10.1002/dc.24564. 2. Finkelstein SD, Sistrunk JW, Malchoff CD, et al. A retrospective evaluation of the diagnostic performance of an interdependent pairwise microRNA expression analysis with a mutation panel in indeterminate thyroid nodules [published online ahead of print, August 9, 2022]. Thyroid. doi:10.1089/thy.2022.0124. 3. Steward DL, et al. JAMA Oncol. 2019;5(2):204-212. 4. Patel KN, et al. JAMA Surg. 2018;153(9):817-824. 5. Banizs AB, et al. Diagn Cytopathol. 2019;47(4):268-274. 6. https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-changes-infographic (accessed 5.20.22) 7. Boufraqech M, et al. Best Pract Res Clin Endocrinol Metab. 2016;30(5):603-619.) 8. Finkelstein SD, Sistrunk JW, Massoll N, et al. Two novel microRNA pairwise expression profilers complement multiplatform molecular testing (MPTX), providing more accurate diagnosis of indeterminate thyroid nodules. Poster presented at: 2021 ATA Annual Meeting; October 2021; online. 9. Ciarletto, AM, Narick, CM, Malchoff, CD, et al. Analytical and Clinical Validation of Pairwise MicroRNA Expression Analysis to Identify Medullary Thyroid Cancer in Thyroid Fine-Needle Aspiration Samples. Cancer Cytopathology. https://doi.org/10.1002/cncy.22365 10. Michaelson G., and Hardin, M. (2010). Pairwise comparisons. In N. J. Salkind (Ed.), Encyclopedia of research design (pp. 985-989). SAGE Publications, Inc., https://dx.doi.org/10.4135/9781412961288.n298 11. Panebianco F, et al. Endocr Relat Cancer. 2019;26(11):803-814. doi:10.1530/ERC-19-0325. 12. Pekova B, et al. Cancers (Basel). 2021;13(8):1932. doi:10.3390/cancers13081932. 13. Liu X. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. 2013 Endocrine-related Cancers, v20 n4 pp603-610 14. Melo, M. TERT Mutations Are a Major Indicator of Poor Outcomes in DTCs, JCEM 2014 15. Yang X, et al. J Nuc Med 2017-TERT Promoter Mutation Predicts I-131 Refractory Character in DTCs 16. Drugs approved for solid tumors anywhere in the body. National Cancer Institute. Updated July 5, 2022. Accessed May 20, 2022. https://www.cancer.gov/about-cancer/treatment/drugs/solid-tumors. 17. Drugs approved for thyroid cancer. National Cancer Institute. Updated January 19, 2021. Accessed May 20, 2022. https://www.cancer.gov/about-cancer/treatment/drugs/thyroid. 18. Cibas E, https://doi.org/10.1089/thy.2017.0500, THYROID Volume 27, Number 11, 2017 19. NCCN guidelines. Version 2.2020, Thyroid Carcinoma – nodule evaluation, THYR-3.
