8172 Retrospective Analysis of mRNA Expression Based Signatures of Thyroid Tumor Invasion and Metastases
Authors: Ahmadi Sara , Namiranian Emma , Alshalalfa Mohammed , Jiang Ruochen , Hao Yangyang , Klopper Joshua P , kloos Richard T , Marqusee Ellen 
Published: October 2024

Abstract
Disclosure: S. Ahmadi: None. E. Namiranian: None. M. Alshalalfa: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R. Jiang: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R.T. kloos: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc.. E. Marqusee: None.
The American Thyroid Association thyroid cancer risk stratification system is driven primarily by the extent of vascular and extrathyroidal extension, as well as lymph node metastases. 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 of clinically significant invasion and metastases with a &gt; 95% negative predictive value as part of the Afirma Genomics Resource for Intelligent Discovery (GRID). 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 thyroid surgery. Two hundred three subjects were evaluated, and pathology reports were scored for the extent of thyroid tumor invasion or metastases. Tumors with extensive vascular invasion or extrathyroidal extension are labeled as high risk (and otherwise are low risk). Tumors with lymph node metastases that either have documented &gt; 2mm tumor deposits, &gt; 40% of central nodes involved, or lateral lymph node metastases are labeled as high risk (and otherwise are low risk). The Afirma GRID invasion and metastases signatures were applied to correlate with the pathology scoring. The cohort was comprised of 144 (70%) female and 59 (30%) male patients with median age of 54 [IQR 40-65]. The cohort was mostly Bethesda III (n= 152, 75%). Fifty three percent (n=109) of the samples were malignant upon histology review. Two samples were scored as high risk for lymph node metastases (LNM) and 4 samples were scored as high risk for invasion (INV) based on final pathology. The LNM signature ruled out 55% of samples with 100% NPV and 55% specificity. No samples with high risk LNM scores were erroneously ruled out by the LNM GRID signature. The rule out % was similar in female (58%) and males (46%) (chi-squared test p=0.1). For the invasion model, 57% of samples were ruled out with 99% NPV and 57% specificity. One sample with extra-thyroidal invasion had a false negative GRID INV signature. The INV rule out % was similar in female (57%) and males (54%) (chi-squared test p=0.19). In summary, the Afirma GRID INV and LNM signatures ruled out clinically significant thyroid tumor features in &gt; 50% of the studied cohort with &gt; 95% NPV. Prospective studies should be performed to confirm the potential for 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.
Presentation: 6/3/2024