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

• DOI: 10.1089/thy.2022.0189
• Publication Date: 2022-07-06T15:32:38Z
• Authors: Gregory W. Randolph; Julie Ann Sosa; Yangyang Hao; Trevor E. Angell; David C. Shonka; Virginia A. LiVolsi; Paul W. Ladenson; Thomas C. Blevins; Quan-Yang Duh; Ronald Ghossein; Mack Harrell; Kepal Narendra Patel; Michael H. Shanik; S. Thomas Traweek; P. Sean Walsh; Michael W. Yeh; Amr H. Abdelhamid...; Allen S. Ho; Richard J. Wong; Joshua P. Klopper; Jing Huang; Giulia C. Kennedy; Richard T. Kloos; Peter M. Sadow
• Keywords: Thyroid Nodules; Surgical pathology

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