A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration.

TitleA panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration.
Publication TypeJournal Article
Year of Publication2012
AuthorsKeutgen XM, Filicori F, Crowley MJ, Wang Y, Scognamiglio T, Hoda R, Buitrago D, Cooper D, Zeiger MA, Zarnegar R, Elemento O, Fahey TJ
JournalClin Cancer Res
Volume18
Issue7
Pagination2032-8
Date Published2012 Apr 01
ISSN1078-0432
KeywordsAdult, Aged, Biomarkers, Tumor, Biopsy, Fine-Needle, Diagnosis, Differential, Female, Humans, Logistic Models, Male, MicroRNAs, Middle Aged, Prospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Sensitivity and Specificity, Support Vector Machine, Thyroid Gland, Thyroid Neoplasms, Thyroid Nodule, Thyroidectomy
Abstract

PURPOSE: Indeterminate thyroid lesions on fine needle aspiration (FNA) harbor malignancy in about 25% of cases. Hemi- or total thyroidectomy has, therefore, been routinely advocated for definitive diagnosis. In this study, we analyzed miRNA expression in indeterminate FNA samples and determined its prognostic effects on final pathologic diagnosis.

EXPERIMENTAL DESIGN: A predictive model was derived using 29 ex vivo indeterminate thyroid lesions on FNA to differentiate malignant from benign tumors at a tertiary referral center and validated on an independent set of 72 prospectively collected in vivo FNA samples. Expression levels of miR-222, miR-328, miR-197, miR-21, miR-181a, and miR-146b were determined using reverse transcriptase PCR. A statistical model was developed using the support vector machine (SVM) approach.

RESULTS: A SVM model with four miRNAs (miR-222, miR-328, miR-197, and miR-21) was initially estimated to have 86% predictive accuracy using cross-validation. When applied to the 72 independent in vivo validation samples, performance was actually better than predicted with a sensitivity of 100% and specificity of 86%, for a predictive accuracy of 90% in differentiating malignant from benign indeterminate lesions. When Hurthle cell lesions were excluded, overall accuracy improved to 97% with 100% sensitivity and 95% specificity.

CONCLUSIONS: This study shows that that the expression of miR-222, miR-328, miR-197, and miR-21 combined in a predictive model is accurate at differentiating malignant from benign indeterminate thyroid lesions on FNA. These findings suggest that FNA miRNA analysis could be a useful adjunct in the management algorithm of patients with thyroid nodules.

DOI10.1158/1078-0432.CCR-11-2487
Alternate JournalClin. Cancer Res.
PubMed ID22351693