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

Autor: Randolph GW; Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.; Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Sosa JA; Department of Surgery, University of California San Francisco (UCSF), San Francisco, California, USA., Hao Y; Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA., Angell TE; Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Shonka DC , Jr; Department of Otolaryngology-Head and Neck Surgery, University of Virginia, Charlottesville, Virginia, USA., LiVolsi VA; Anatomic Pathology Division, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA., Ladenson PW; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA., Blevins TC; Texas Diabetes and Endocrinology, Austin, Texas, USA., Duh QY; Section of Endocrine Surgery, Department of Surgery, University of California San Francisco, San Francisco, California, USA., Ghossein R; Department of Pathology and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA., Harrell M; The Memorial Center for Integrative Endocrine Surgery, Hollywood, Weston and Boca Raton, Florida, USA., Patel KN; Division of Endocrine Surgery, Department of Surgery, NYU Langone Medical Center, New York, New York, USA., Shanik MH; Endocrine Associates of Long Island, Smithtown, New York, USA., Traweek ST; Thyroid Cytopathology Partners, Austin, Texas, USA., Walsh PS; Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA., Yeh MW; Section of Endocrine Surgery, UCLA David Geffen School of Medicine, Los Angeles, California, USA., Abdelhamid Ahmed AH; Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA., Ho AS; Department of Otolaryngology, Cedars-Sinai Medical Center, Los Angeles, California, USA., Wong RJ; Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Klopper JP; Department of Medical Affairs, Veracyte, Inc., South San Francisco, California, USA., Huang J; Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA., Kennedy GC; Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA.; Department of Medical Affairs, Veracyte, Inc., South San Francisco, California, USA., Kloos RT; Department of Medical Affairs, Veracyte, Inc., South San Francisco, California, USA., Sadow PM; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Massachusetts Eye and Ear, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Thyroid : official journal of the American Thyroid Association [Thyroid] 2022 Sep; Vol. 32 (9), pp. 1069-1076. Date of Electronic Publication: 2022 Aug 08.
DOI: 10.1089/thy.2022.0189
Abstrakt: 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 MTC-specific preoperative evaluation and resulting treatment.
Databáze: MEDLINE