Multicenter, retrospective, blinded validation study of 309 subjects with indeterminate thyroid nodules (Bethesda III, IV, or V) and corresponding surgical histology. Gold-standard unanimous consensus histopathology diagnosis (n=197) among three pathologists was used, and all molecular testing was performed using archived cytology smears. Results were reported in 3 categories (negative, moderate, or positive) based on the combined test results from both ThyGeNEXT® (mutation panel) and ThyraMIR® (microRNA risk classifier). The proportion of benign and malignant histopathologic subtypes within this study vastly differed from those found within a recent prospective study.1,2 Histopathologic subtype prevalence adjustments were used to determine the impact of these differences on test performance.3 The analysis showed that test performance was optimal after prevalence adjustments.
The 3-category microRNA and mutation panel combination test had a high PPV (positive predictive value) at 75% and high NPV (negative predictive value) at 97% (n=178) after prevalence adjustments.1 Prevalence-unadjusted, PPV and NPV were 74% and 95%, respectively, for the 3-category approach.1
microRNA classification further risk-stratified patients with weak driver mutations, including RAS, resulting in four out of five nodules being accurately ruled-in or ruled-out for disease.1
1. Lupo MA, et al. Diagn Cytopathol. 2020;1–11. https://doi.org/10.1002/dc.24564 2. Steward DL, et al. JAMA Oncol. 2019;5(2):204-212. 3. Usher-Smith JA, et al. BMJ. 2016;353:i3139.
