Retrospective Analysis of mRNA Expression Based Signatures of Thyroid Tumor Invasion and Metastases

Introduction

• The American Thyroid Association thyroid cancer initial risk stratification system is driven primarily by the extent of vascular and extrathyroidal extension, as well as the presence of lymph node metastases.¹
• Minimizing surgical intervention for thyroid tumors from indeterminate thyroid nodules (ITN – Bethesda III and IV cytology) is often preferred to mitigate surgical complications and lessen the need for thyroid hormone supplementation post-operatively if clinical outcomes are not worsened.
• By leveraging the whole transcriptome derived Afirma Genomic Sequencing Classifier (GSC) thyroid nodule molecular testing platform, mRNA expression-based signatures were developed to predict thyroid tumors with a low risk (>95% NPV) of clinically significant invasion and metastases, as part of the Afirma Genomics Resource for Intelligent Discovery (GRID).²
• The objective of this study was to analyze the performance of these signatures on a retrospective cohort of patients with ITN who had Afirma GSC-suspicious findings and then underwent thyroid surgery.

Conclusion

• These data confirm the ability of the Afirma GRID INV and LNM signatures to effectively rule out clinically significant higher-risk tumor features in >50% of the studied cohort with >95% NPV.
• The low prevalence of aggressive histology from nodules with indeterminate cytology makes development of a rule in signature for aggressive disease very challenging.
• Prospective studies should be performed to confirm the utility of Afirma GRID tumor behavior signatures to optimize and individualize surgical decision-making, decreasing the burden of unnecessary extent of thyroid surgery while maintaining outstanding clinical outcomes.
• Future research opportunities include developing tumor behavior signatures for lesions with Bethesda V/VI cytology and/or a BRAFV600E mutation.