Although most thyroid nodules with indeterminate cytology are benign, in most of the world surgery remains as the most frequent diagnostic management. We have previously reported a 10-gene thyroid genetic classifier which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology.Classifier performance was tested in two independent, ethnically diverse, prospective, multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to pathology report. A matched surgical pathology and valid classifier score was available for 270 samples.Cohorts showed significant differences including; i) clinical site patient source (academic, 43% and 97% for TGCT-1 and 2, respectively), ii) ethnic diversity, with greater proportion of Hispanic (40% vs 3%) for TGCT-1 and greater proportion of African-American (11% vs 0%) and Asian (10% vs 1%) population for TGCT-2, and iii) tumor size, (mean of 1.7 cm and 2.5 cm for TGCT-1 and -2, respectively). Overall, there were no differences in the histopathological profile between cohorts. Forty-one of 155 and 45 of 115 nodules were malignant (cancer prevalence of 26% and 39% for TGCT 1 and 2, respectively). The classifier predicted 37 of 41 and 41 of 45 malignant nodules, yielding a sensitivity of 90% (95% confidence interval CI 77-97%) and 91% (95% CI 79-98%) for TGCTs 1 and 2, respectively. One hundred and one of 114 and 61 of 70 nodules were correctly predicted as benign yielding a specificity of 89% (95% CI 82-94%) and 87% (95% CI 77-94%), respectively. The negative predictive values for TGCT-1 and TGCT-2 were 96% and 94%, respectively, whereas the positive predictive values were 74% and 82%, respectively. The overall accuracy for both cohorts was 89%.Clinical validation of the classifier demonstrates equivalent performance in two independent and ethnically diverse cohorts, accurately predicting benign thyroid nodules that can undergo surveillance as an alternative to diagnostic surgery.
View details for DOI 10.1089/thy.2019.0490
View details for PubMedID 31910118