New research presented at ENDO 2024

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

By performing whole-transcriptome derived analysis on each thyroid FNA sample that Veracyte receives, a tremendous amount of data is generated on every nodule.¹ This creates the potential for novel research, such as the two tumor behavior signatures examined in this study. The first of these signatures is the invasion signature, which predicts the risk of a tumor lacking clinically significant vascular or extra-thyroidal invasion. The second signature predicts the risk of a tumor lacking clinically significant lymph node metastases.

This study evaluated the performance of these two predictive signatures among a cohort of 203 patients with cytologically indeterminate nodules with Afirma GSC Suspicious results that ultimately underwent thyroid surgery, 152 of which were Bethesda III and 51 of which were Bethesda IV.

Ultimately, this study confirmed the ability of these two signatures to rule out significant tumor features with >95% NPV in over half of the studied cohort. Specifically, the invasion signature ruled out 57% of the samples with a 99% NPV and 57% specificity, and the lymph node metastases signature ruled out 55% of the samples with a 100% NPV and 55% specificity.

Prostate-Specific Membrane Antigen (PSMA) Expression in Cytologically Indeterminate and Malignant Thyroid Nodules

Prostate-specific membrane antigen (PSMA), a transmembrane protein encoded by FOLH1, is a receptor expressed in a variety of solid tumors. This study aimed to characterize PSMA expression in a large cohort of thyroid nodules. FOLH1 (PSMA) mRNA expression was analyzed across 47,695 thyroid nodules sent for Afirma Genomic Sequencing Classifier (GSC) molecular testing.

Here’s what this study found:

• PSMA expression was found to be higher among GSC Suspicious and BV/VI nodules than GSC Benign nodules
• Samples with PAX8-PPARG, ALK/RET fusions had higher PSMA expression than GSC Benign
• Samples with TSHR variants had the lowest PSMA expression in both GSC Suspicious and Bethesda V/VI samples

This study demonstrates PSMA expression may provide further thyroid tumor prognostic information, though the basis for increased PSMA expression in the setting of PPARG and other fusions is an opportunity for future investigation, as are the roles of preoperative assessment of PSMA expression and PSMA-based imaging and therapy in the setting of advanced thyroid cancer.

Cancer-associated Fibroblasts Correlate with Aggressive Thyroid Cancer Behavior: Insights from Four Large Patient Cohorts

Recently, immune signatures that included the detection of cancer-associated fibroblasts have been identified as a predictor of aggressive thyroid cancer.² These fibroblasts have yet to be analyzed in thyroid tumor FNA samples, however. In this study, associations between CAF gene signatures and tumor characteristics were explored across 4 large cohorts:

• A 47,695 sample Afirma GSC cohort
• A 318 sample retrospective FNA cohort from Memorial Health System with pathology outcome data
• A cohort of 496 papillary thyroid cancers from TCGA
• A 312 sample resection cohort from Vanderbilt University Medical Center-University of Washington

In this study, a novel thyroid-cancer specific CAF gene signature was created and the ability to detect a thyroid-cancer specific CAF gene signature in thyroid FNAs was demonstrated across these cohorts. In addition, certain CAF subsets demonstrated prognostic potential: specifically, SFRP2+ CAFs were found to be associated with aggressive characteristics such as shorter progression-free survival, tumor invasion, and lymph node metastases.

Conclusion

We’re happy that Veracyte could take part in the research presented at ENDO, and we feel that this research serves as a great example of what’s possible with Afirma GRID. If you have questions about the Afirma GRID platform or are interested in collaborating with us, fill out the form below.