Preoperative Identification of Medullary Thyroid Carcinoma (MTC): Clinical Validation of the Afirma MTC RNA-Sequencing Classifier

作者：Gregory William Randolph, Julie Ann Sosa, Yangyang Hao, Trevor E. Angell, David C. Shonka, Virginia A. LiVolsi, Paul W. Ladenson, Thomas Blevins, Quan‐Yang Duh, Ronald A. Ghossein, Mack Harrell, Kepal Narendra Patel, Michael Howard Shanik, S. Thomas Traweek, P. Sean Walsh, Michael W. Yeh, Amr H. Abdelhamid Ahmed, Allen S. Ho, Richard J. Wong, Joshua P. Klopper, Jing Huang, Giulia Catignani Kennedy, Richard T. Kloos, Peter M. Sadow · 发表于：Thyroid · 年份：2022 · DOI：10.1089/thy.2022.0189 · 被引用次数：30 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Genetic factors in colorectal cancer、Biomedical Text Mining and Ontologies

Background: Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III–VI). In this study we report the development and clinical performance of this MTC classifier. Methods: Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette. Results: The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI] = 83.9–100%) and 100% specificity (190/190 non-MTC FNAs correctly called negative; CI = 98.1–100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology. Conclusions: The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an M...