Nikiforova, Marina N.1; Mercurio, Stephanie1; Wald, Abigail I.1, Santana dos Santos, Lucas1, Barbi De Moura, Michelle1, Roy, Somak1; Nikiforov, Yuri E.1
1 Department of Pathology, University of Pittsburgh, Pittsburgh, PA., USA
Background /Purpose: Ancillary molecular testing contributes to more accurate cancer diagnosis in thyroid nodules with indeterminate FNA cytology. Most impactful molecular tests should have high sensitivity and specificity of cancer detection in all types of thyroid nodules. The goal of this study was to perform validation of the ThyroSeq v3 test in a large series of lesions representing all types of thyroid pathology.
Methods: ThyroSeq v3 is based on the next-generation sequencing analysis of 112 genes for point mutations, gene fusions, gene expression, and copy number changes. The performance of this test was evaluated in a series of 239 surgically removed thyroid samples and 122 FNA samples. The former included 64 PTC, 36 oncocytic FTC, 11 conventional FTC, 14 MTC and 6 PDC/ATC, as well as 20 adenomas, 34 hyperplasias, 6 Hashimoto thyroiditis, 13 parathyroid nodules and 19 non-thyroidal cancers.
Results: In this study cohort, ThyroSeq v3 detected 134 out of 138 cancers, resulting in the sensitivity of 97.1% and specificity of 82.2%. Specifically, the test correctly identified 62 out of 64 PTC, 29 out or 30 oncocytic FTC, and 10 out of 11 conventional FTC. In addition, 14/14 MTC and 13/13 parathyroid nodules were correctly identified. False-negative cases included 1 follicular variant and 1 classical PTC, as well as 1 minimally-invasive oncocytic FTC and 1 angioinvasive conventional FTC.
Discussion & Conclusion: An expanded ThyroSeq v3 test demonstrated high sensitivity and specificity of cancer detection, including the detection of oncocytic follicular carcinomas, medullary carcinomas, and parathyroid and other non-thyroid nodules.