Molecular Profiling of Black and White Patients With Indeterminate Thyroid Nodules

Introduction

• Black patients with thyroid cancer experience disproportionately poorer outcomes compared to White counterparts.
• While potentially linked to delayed diagnosis and systemic barriers, it remains unclear whether biologic differences contribute.
• Our aim is to explore race-associated molecular differences in indeterminate thyroid nodules (ITN) sent for molecular testing and assess whether they may contribute to observed disparities.

Methods

• Study Design
  • Retrospective cohort (2017-2023)
  • 135 patients: Black (n=65), White (n=70)
  • Thyroid nodule FNA → surgical evaluation
• Data Collection
  • Genomic variables: Afirma GSC classification (Benign vs. Suspicious), Xpression Atlas alterations
  • Expression signatures: EMT, NIS, ERK, TDS
• Study Outcomes
  • Afirma GSC molecular and Genome-wide differential expression analysis by race
  • Public external data: MSK-IMPACT® and AACR-GENIE®

Results

• Black patients’ thyroid cancers are relatively enriched in RAS family mutations.
• In this cohort referred for surgery, the overall Afirma GSC-S rate is higher than the overall expected rate of ~65%.
• This appears to mainly be driven by the high rate of Afirma GSC-S results (83%) in White patients.
• White patients had more expressed alterations than Black patients.
• There was trend toward higher BRAFV600E in Whites vs Blacks.
• Black patients had significantly lower expression of the EMT pathway, TDS, and NIS.
• TUBB2A was the highest differentially expressed genes in Black patients, F8A1 was the lowest.

Conclusion

• White patients:↑ detectable XA variants, trend toward ↑ BRAFV600E positivity, ↑ EMT expression.
• Black patients: ↓ TDS, ↑ NRAS,↓ NIS.
• This work highlights the need to further examine racial influences on tumor biology amid underrepresentation of Black patients in genomic datasets.