Diagnostic Value of Circulating microRNA-95 and -190 in the Differential Diagnosis of Thyroid Nodules: A Validation Study in 1000 Consecutive Patients.

Abstract

It has recently been demonstrated that the combination of miRNA-190 and -95 (expressed as probability of malignant risk: pmiRNA) in the serum of Caucasian patients with thyroid nodular disease allows the identification of nodules at high risk of malignancy with great accuracy. The present study aimed to validate these results in a larger cohort of patients. This study prospectively analyzed 1000 patients. Cytological diagnosis was available in 982/1000 (98.2%) and histological diagnosis in 445/1000 (44.5%). The expression levels of circulating miRNA-190 and -95 were determined by real time polymerase chain reaction with the 2-ΔΔct method. The diagnostic performance (sensitivity, specificity, and accuracy) of fine-needle aspiration cytology (FNAC), pmiRNA, and a combination of the two methods was correlated with the cytological and histological diagnoses. The combination of pmiRNA and FNAC significantly increased the sensitivity (96.3%) with respect to each method alone (88.9% for FNAC and 89.6% for pmiRNA) by reducing the rate of false-negative results from 18 for FNAC and 17 for pmiRNA to only five. In patients in whom FNAC was not performed (n = 14) or in those with inadequate (n = 18) or indeterminate (n = 72) lesions submitted to surgery, pmiRNA correctly identified 90.8% of patients with benign disease and 74.3% of patients with cancer. These results confirm that a combination of serum expression levels of miRNA-95 and -190 is an accurate and noninvasive tool for the differential diagnosis of thyroid nodules in the Italian population.