González, Hernán E.1, Martínez, José R.1, Vargas-Salas, Sergio1, Solar, Antonieta2, Cruz, Francisco3, Arias , Tatiana3, Loyola, Soledad3, Dominguez, José Miguel4 , Horvath , Eleonora5, Tala, Hernán5, Traipe, Eufrosina6, Meneses, Manuel6, Marín, Luis6, Wohllk, Nelson7, Diaz , René E.7, , Jesús Véliz7, Pineda, Pedro8, Arroyo, Patricia9, Lobos, Maite10, Medina, Francisco11 , Lobos, Germán11, Osorio, Miren11, Schatcher, Dina11, Glacinovic, Andrea11, Mena, Natalia12, González, Claudia12, Miranda, Giovanna12, Bruce, Elsa12 , Urra, Soledad1.
1 Department of Surgical Oncology, 2 Department of Anatomic Pathology, 3 Department of Radiology, 4Department of Endocrinology, Faculty of Medicine Pontificia Universidad Católica de Chile, Santiago, Chile
5 Department of Radiology, Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile
6 Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile
7 Department of Endocrinology, Hospital del Salvador, Universidad de Chile, Santiago, Chile
8 Sección Endocrinología y Diabetes, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile
9 Hospital San Juan de Dios, Santiago, Chile
10 Centro Diagnóstico Plaza Italia, Santiago Chile
11 Department of Radiology, Clínica Santa María, Santiago, Chile
12 GeneproDX Chile SpA, Santiago, Chile.
Background: In most of the world, diagnostic surgery remains as the most frequent approach for treatment of indeterminate thyroid nodules (ITN). Although, several molecular tests are available for central-lab testing in the US, there are no available diagnostic kits for local laboratory testing. To address this issue, we have developed and performed a clinical validity study of a 10-gene thyroid genetic classifier In Vitro Diagnostic test (TGC-IVD) for ITN with a level of complexity such that it may be used in reference laboaratories.
Methods: We performed a 21-month, prospective, double-blinded, multi-center clinical validation study including 9 institutions, 2648 patients, 2982 fine-needle aspirations of which 565 (18,9%) were indeterminate (Bethesda III & IV). At the time of this analysis, the corresponding surgical pathology and adequate RNA was obtained for 193 samples. The expression of 10 genes was analyzed using a multiplexed q-PCR TGC-IVD and its performance was evaluated.
Results: Of the 193 ITNs, 51 were malignant (cancer prevalence of 25.4%). The TGC-IVD correctly identified 47 of 51 malignant nodules, with a sensitivity of 92.2% (CI of 87-98%), and specificity of 90.8% (95% CI of 84-96%). The negative predictive values ??for follicular lesion or atypia of undetermined significance (Bethesda III) and follicular neoplasm (Bethesda IV) were 97.6% and 96.7%, respectively, whereas the positive predictive values ??were 77.8% And 78.6%, respectively. The TGC-IVD correctly predicted a case of medullary thyroid cancer as malignant.
Conclusions: We report the clinical validation of a new TGC-IVD that accurately predicts the nature of indeterminate thyroid nodules and could be a future solution suitable for local reference laboratory testing, providing an accesible solution for clinicians to identify patients that can avoid diagnostic surgery.