Interpace, Affirma, and Thyroseq Performance Characteristics in 341 Bethesda Category III/IV Thyroid Nodules

Abstract

Abstract Introduction/Objective Multiple FDA-approved molecular testing platforms are used by our institution for evaluating genomic characteristics of thyroid nodules. We aim to correlate molecular results and final histopathology (HPE) of thyroid nodules with cytologic diagnosis of The Bethesda System (TBS) Category III or IV. Methods/Case Report We included 341 cases of thyroid nodules diagnosed as TBS-III or TBS-IV with subsequent molecular analysis performed on 1 of 5 platforms (Interpace ThyraMIR Thyroid miRNA Classifier, Afirma Genomic Sequencing Classifier, Thyroseq Genomic Classifier, Next-Generation Sequencing (NGS) Fusion Panel, or RosettaGX Reveal Thyroid miRNA Classifier). All findings reported on molecular analysis and all benign or malignant neoplasms diagnosed on final HPE were considered “significant findings.” Performance characteristics of all 5 molecular platforms were analyzed. Results (if a Case Study enter NA) Of 341 cases, 80.1% (n=273) were classified as TBS-III and 19.9% (n=68) were classified as TBS-IV. The overall concordance of molecular and final HPE when available was 60.9% (n=28). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) are respectively 75.0%, 60.0%, 75.0%, and 60.0% for Interpace; 65.0%, 60.0%, 85.0%, and 33.0% for Afirma; and 75.0%, 50.0%, 75.0%, and 50.0% for Thyroseq platforms. Of TBS-III cases, 66.3% (n=181), 25.6% (n=70), 4.8% (n=13), 1.5% (n=4), and 1.8% (n=5) underwent molecular testing via Interpace, Afirma, Thyroseq, NGS, and Rosetta platforms, respectively. Only 9.2% (n=25) of TBS-III cases had subsequent HPE. Concordance of molecular and final HPE for TBS-III cases was 52.0% (n=13) with a PPV of 75.0% and NPV of 40.0%. Concordances of molecular and final HPE according to molecular platform are: 57.1% (n=4) on Interpace, 53.3% (n=8) on Afirma, and 50.0% (n=1) on Thyroseq. Of TBS-IV cases, 52.9% (n=36), 36.8% (n=25), 5.9% (n=4), 2.9% (n=2), and 1.5% (n=1) underwent molecular testing via Interpace, Afirma, Thyroseq, NGS, and Rosetta platforms, respectively. Only 30.9% (n=21) of TBS-IV cases had subsequent HPE. Concordance of molecular and final HPE for TBS-IV cases was 71.4% (n=15) with a PPV of 86.0% and NPV of 43.0% Concordances of molecular and final HPE according to molecular platform are: 71.4% (n=5), 66.7% (n=6), and 75.0% (n=3) on Interpace, Afirma, and Thyroseq respectively. Conclusion Our study reports similar performance characteristics of 3 commonly used molecular platforms (Interpace, Afirma, and Thyroseq) for genomic evaluation of thyroid nodules.