Veracyte, Inc. announced new research findings suggesting the potential of novel molecular signatures to identify patients with thyroid nodules or cancer who have aggressive disease. The findings, which could potentially help clinicians further individualize care based on each patient's tumor biology, are derived from research using Veracyte's Afirma GRID (Genomic Resource for Intelligent Discovery) tool. The results were presented at ENDO 2024, the annual meeting of The Endocrine Society in Boston.

Following are highlights of the three Afirma GRID-focused studies presented at the ENDO 2024 conference: Poster presentation (MON-640): Retrospective Analysis of mRNA Expression Based Signatures of Thyroid Tumor invasion and Metastases. presented by Sara Ahmadi, M.D., Brigham and Women's Hospital. Summary: Researchers analyzed novel whole-transcriptome-based signatures, previously presented at the ENDO 2023 meeting, that were designed to help rule out significant thyroid tumor invasion or regional lymph node metastases in patients with indeterminate thyroid nodules.

This was a retrospective study of 203 thyroid nodule patients with indeterminate cytology who had Afirma GSC-suspicious results and pathology results from subsequent thyroid surgery. The molecular signatures ruled out the clinically significant features in more than 50% of patients, with a greater than 95% negative predictive value. Oral presentation (OR28-04): Cancer-associated Fibroblasts Correlate with Aggressive Thyroid Cancer Behavior: Insights from Four Large Patient Cohorts.

Presented by Matthew A. Loberg, B.A., Vanderbilt University Medical Center. Summary: Researchers identified cancer-associated fibroblasts (CAFs) in the thyroid tumor microenvironment that correlate with aggression in thyroid cancers largely by leveraging the Afirma GRID database, which includes whole-transcriptome data derived from the Afirma assay. In this multicenter study involving nearly 50,000 patients, they identified CAFs for the first time in pre-operative fine needle aspiration (FNA) samples.

Notably, they found that the SFRP2+ CAF was associated with shorter progression-free survival, tumor invasion and lymph node metastasis. It was also enriched in thyroid nodules that were deemed suspicious by the Afirma Genomic Sequencing Classifier (GSC) or Bethesda V/VI by cytopathology, compared to Afirma GSC-benign nodules. While more study is needed, such insights could potentially help inform more-personalized management strategies for patients with thyroid nodules or cancer.

Poster Presentation (MON-649) and Rapid-Fire Oral Presentation (RF28-01): Prostate-specific Membrane Antigen (PSMA) Expression in Cytologically Indeterminate and Malignant Thyroid Nodules. Presented by Rabail Sadiq, M.B.B.S., Johns Hopkins University School of Medicine. Prostate-specific membrane antigen (PSMA) is a protein found on the surface of cancer cells and is increasingly used as a biomarker in prostate cancer detection and treatment.

Higher PSMA levels have also been associated with more-aggressive thyroid cancers. Researchers leveraged the Afirma GRID database to characterize the expression of PSMA (FOLH1) in a cohort of nearly 50,000 thyroid nodules sent for Afirma GSC molecular testing. They found that PSMA gene expression was higher in indeterminate nodules that were Afirma GSC-suspicious and in nodules whose cytopathology was classified as Bethesda V/VI, compared to Afirma GSC-benign nodules.

They also found variability in PSMA expression in the context of certain molecular driver mutations. The authors conclude that PSMA expression may potentially help provide further prognostic information to inform care for thyroid nodule patients.