Background
Following malignancy risk stratification by ultrasound, the current gold standard for the differential diagnosis of thyroid nodules is Fine Needle Aspiration Cytology (FNAC). However, in 20-30% of nodules FNAC is hampered by an inherent limitation that results in “indeterminate” categories that require a diagnostic lobectomy for diagnosis. Thus, every year thousands of Canadian patients are exposed to invasive and often unnecessary diagnostic surgery due to a lack of more elegant tools to address suspicion of thyroid cancer.
ThyroSPEC™
ThyroSPEC™ offers an opportunity to overcome these limitations and reduce the patient burden, complications, and cost of managing thyroid nodules and thyroid cancer. As an adjunct to an optimised thyroid nodule diagnostic pathway with ultrasound thyroid nodule malignancy risk stratification and thyroid nodule cytology ThyroSPEC™ contributes to the malignancy risk stratification of indeterminate thyroid nodules to inform shared clinical decision making (follow up vs lobectomy vs total thyroidectomy).
ThyroSPEC™ is a proprietary, highly accurate, cost-efficient MALDI-TOF mass spectrometry-based mutation detection panel that detects the most prevalent 138 point mutations and gene fusions reported in thyroid cancer in the following genes:
| Genes (number of mutations) | Fusions (number of fusions) |
| AKT1 (1) | AGK::BRAF (1) |
| BRAF (7) | AKAP9::BRAF (1) |
| CTNNB1 (11) | CCDC6::RET (1) |
| DICER1 (3) | CRTC1::MAML2 (1) |
| EGFR (1) | EML4::ALK (1) |
| EIF1AX (4) | ETV6::NTRK3 (1) |
| EZH1 (1) | IGF2BP3::THADA (1) |
| HRAS (15) | NCOA4::RET (1) |
| IDH1 (1) | PAX8::PPARG (4) |
| KRAS (17) | PRKAR1A::RET (1) |
| NRAS (15) | RET::GOLGA5 (1) |
| PIK3CA (5) | RPS2P32::THADA (1) |
| PTEN (1) | SND1::BRAF (1) |
| RET (19) | SQSTM1::NTRK3 (1) |
| SPOP (1) | STRN::ALK (1) |
| TERT (c.1-124C>T, c.1-146C>T) | TFG::NTRK1 (1) |
| TP53 (10) | TMEM233::PRKAB1 (1) |
| TSHR (2) | TPM3::NTRK1 (1) |
| TPR::NTRK1 (1) |
ThyroSPEC™ inputs include residual DNA and RNA extracted from liquid FNAC material after preparation of slides, or air-dried FNAC smear, or FFPE of resected tissue. A separate pass is not required which means ThyroSPECTM does not necessitate changing the local thyroid nodule fine needle cytology practice.
Highly multiplexed genotyping on the MassARRAY MS platform (Agena Biosciences) is faster and has much lower cost per sample than next generation sequencing.
Ordering ThyroSPECTM
Alberta Precision Laboratories has implemented ThyroSPECTM as a reflex test for indeterminate thyroid FNACs in Alberta.
Alberta Precision Laboratories also offers ThyroSPECTM for out of province samples as a commercial test. To order the test the following is required:
– completion of the APL Molecular Pathology requisition,
– payment information,
– sample sent to APL for testing as per sample guidelines.
For more information: contact@thyrospec.com
Referral possibilities for patients with indeterminate FNA cytology and additional ThyroSPEC™ testing
Referral possibilities for patients with indeterminate FNA cytology and additional ThyroSPEC™ testing in Alberta, Canada can be found at the Alberta Health Services Guideline Resource Unit (GURU) webpage.
The Paschke & Eszlinger Lab 