Background
Clinicians in Canada are currently faced with a lack of tools along the clinical care pathway that are needed to appropriately risk stratify patients who present with thyroid nodules. 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.
Modern molecular diagnostic tests offer an opportunity to overcome these limitations and reduce the patient burden, complications, and cost of managing thyroid nodules and thyroid cancer. Molecular diagnosis risk stratifies these indeterminate nodules for clinical decision making (follow up vs lobectomy vs total thyroidectomy).
ThyroSPEC™
ThyroSPEC™ is a proprietary, highly accurate, cost-efficient MALDI-TOF mass spectrometry-based mutation detection panel that detects the most prevalent 117 point mutations and 23 gene fusions reported in thyroid cancer in the following genes:
| Point Mutations | Rearrangements | Gene Expression Cassette |
| AKT1 | ALK | PGK1 |
| BRAF | BRAF | TTF1 |
| CTNNB1 | MAML2 | KRT20 |
| DICER1 | NTRK1 | CALCA |
| EGFR | NTRK3 | KRT7 |
| EIF1AX | PPARG | PAX8 |
| EZH1 | PRKAB1 | TG |
| HRAS | RET | PTH |
| IDH1 | THADA | |
| KRAS | ||
| NRAS | ||
| PIK3CA | ||
| RET | ||
| SPOP | ||
| TERT | ||
| TP53 | ||
| TSHR |
ThyroSPEC™ inputs include DNA and RNA extracted from residual 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 aspiration 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 will also offer this test for out of province samples as a commercial test. For more information: contact@thyrospec.com
Questions concerning the further clinical interpretation of ThyroSPEC™ results can be addressed to Dr. Ralf Paschke (ralf.paschke@albertahealthservices.ca)
Referral possibilities for patients with indeterminate FNA cytology and additional ThyroSPEC™ testing in the AHS Calgary Health Care Region can be found at the Alberta Health Services webpage: https://www.albertahealthservices.ca/assets/info/hp/cancer/if-hp-cancer-guide-molecular-fna-report.pdf
The Paschke & Eszlinger Lab 