Combination Testing
ThyGeNEXT + ThyraMIR is the only testing platform that utilizes both mutational and microRNA markers to aid patient management
Why Combination Testing?
- Not all mutations are strongly predictive of malignancy1
- Strong driver mutations, such as BRAF V600E, TERT promoter, and RET fusions have proven useful in surgical decision-making2-9
- Weak driver mutations, such as RAS or PAX8/PPAR, carry less certainty10,11
Variable PPV of RAS Mutations
- RAS mutations are common in adenomas13
- PPV of RAS mutations can vary due to differences in risk of malignancy among histopathologic subtypes14
“Mutations strongly associated with malignancy, such as BRAF V600E, RET fusions, and TERT, can assist in surgical decision-making. Other mutations considered weak drivers of cancer, such as RAS, carry less certainty.”12
ThyGeNEXT + ThyraMIR Testing Algorithm*1,12
Patient Management
- Strong driver mutations, such as BRAF V600E, TERT promoter, and RET/PTC help inform consideration of surgical intervention2-9
- microRNA classification assists with variable mutational profiles
- Lack of detectable mutations1
- Weak driver mutations, such as RAS1,12
*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 test positive for markers that have a lower risk of malignancy, such as RAS, will also receive a ThyraMIR report.
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.
NCCN guidelines for management of nodules with B3 and B4 cytology diagnoses include consideration of molecular analysis.15
Markers that MatterTM
Strategically Designed Mutation Panel for the Optimal Management of Thyroid Nodules
| DNA mutation panel | RNA panel (# 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 |
- BRAF V600E, TERT promoter, and ALK mutations can reliably help predict aggressive biological features of thyroid cancer8,13,16
| FTC | PTC | PDTC | ATC | MTC | |
|---|---|---|---|---|---|
| Upregulated | miR-222-3p | miR-222-3p | miR-222-3p | miR-222-3p | miR-375 |
| miR-146b-5p | miR-146b-5p | miR-146b-5p | miR-146b | ||
| miR-31-5p | miR-551b | ||||
| Downregulated | MiR-139-5p | miR-204-5p | miR-204-5p | miR-138-1-3p | |
| miR-155-5p | miR-29b-1-5p | ||||
| miR-155-5p |
- miRNAs can help rule in all types of thyroid cancers17,18
References
1. Banizs AB, et al. Diagn Cytopathol. 2019;47(4):268-274. 2. Liu T, et al. Oncogene. 2014;33(42):4978-4984. 3. Landa I, et al. J Clin Endocrinol Metab. 2013;98(9):E1562-1566. 4. Nikiforov YE, et al. J Clin Endocrinol Metab. 2011;96(11):3390-3397. 5. Santoro M, et al. Cold Spring Harb Perspect Biol. 2013;5(12):a009233. 6. Liu X, et al. Endocr Relat Cancer. 2013;20(4):603-610. 7. Fussey JM, et al. Clin Endocrinol (Oxf). 2019;91(6):697-707. 8. Melo M, et al. J Clin Endocrinol Metab. 2014;99 (5):E754-765. 9. Censi S, et al. Eur J Endocrinol. 2019;181(1):1-11. 10. Marcadis AR, et al. Surgery. 2019;165(1):17-24. 11. Guan H, et al. Thyroid. 2020;30(4):536-547. 12. Lupo MA, et al. Diagn Cytopathol. 2020;1-11. https://doi.org/10.1002/dc.24564. 13. Liu R, et al. Endocr Relat Cancer. 2016;23(3):R143-R155. 14. Nabhan F, et al. Thyroid. 2018;28(6):729-738. 15. NCCN guidelines. Version 2.2020, Thyroid Carcinoma – nodule evaluation, THYR-3. 16. Bae JS, et al. Diagn Pathol. 2016;11:21. 17. Visone R, et al. Oncogene. 2007;26(54):7590-7595. 18. Nikiforova MN, et al. J Clin Endocrinol Metab. 2008;93(5):1600-1608.
