Cancer Prognostication Using Thyroseq V3

A unique feature of ThyroSeq as compared to other molecular tests for thyroid FNA samples is that, in addition to the diagnostic utility:
- It provides information that helps to prognosticate cancer pre-operatively
Based on the current thyroid cancer management guidelines from the ATA, cancer risk stratification is important in:
- Determining the appropriate extent of surgery (lobectomy vs total thyroidectomy ), radioactive iodine (RAI) administration, and intensity of follow-up
Most thyroid cancers are indolent and these patients are at low risk for disease recurrence after cancer removal:
- These patients can be treated by lobectomy and are unlikely to benefit from RAI ablation and TSH suppression
Similarly, surgical excision of a pre-cancer tumor:
- NIFTP, by lobectomy is likely to be curative since the risk of tumor recurrence is less than 1%
On the other hand, patients with high-risk cancers would benefit from up-front total thyroidectomy:
- Which facilitates post-operative RAI administration and disease monitoring
ThyroSeq is the only molecular test that provides cancer risk assessment pre-operatively based on the analysis of multiple mutational markers associated with cancer prognosis

Specifically, finding of single RAS mutations or RAS-like mutations without other higher-risk mutations tested by ThyroSeq is associated with:
- A low risk for recurrence
Whereas identification of isolated BRAF V600E and other BRAF V600E-like mutations is associated with:
- An intermediate risk for disease recurrence (Yip et al. Ann Surg, 2015)
Identification of TERT promoter mutations, and specifically the co-occurrence of TERT with other, early driver mutations or finding of multiple cancer driver mutations is associated with:
- A high risk for cancer recurrence (Nikiforov YE. Endocrine Practice, 2017)
Importantly, cancer prognostication requires the analysis of all genes associated with thyroid cancer behavior which are included in the ThyroSeq panel
- For example, the finding of RAS mutation by a small panel of genes carries no prognostic information, because while an isolated RAS mutation confers a low risk of disease reoccurence:
  - The coexistence of RAS with TERT or TP53 gene mutations is a molecular signature of a high-risk cancer (Nikiforova et al. 2016)
In addition, the ThyroSeq test is able to diagnose a high-risk cancer in nodules which may be very small and have no particularly worrisome ultrasonographic features:
- As an illustration, a tumor as small as 0.6 cm may already have a molecular signature of aggressive thyroid cancer developed (Shrestha RT et al. Thyroid. 2015)

Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO