Abstract
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. 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. 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. 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.
Highlights
Thyroid cancer is the most common endocrine neoplasm
When applied to the 72 independent in vivo validation samples, performance was 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
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 fine needle aspiration (FNA)
Summary
Thyroid cancer is the most common endocrine neoplasm. Its incidence is increasing and females are affectedAuthors' Affiliations: 1Division of Endocrine Surgery, Department of Surgery, 2Department of Pathology, 3Institute for Computational Biomedicine, New York Presbyterian Hospital–Weill Cornell Medical Center, New York; 4Section of Endocrine Surgery, Department of Surgery, and 5Division of Endocrinology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MarylandNote: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).Presented in part at the 97th Annual Meeting of the American College of Surgeons in San Francisco (CA), October 2011 and at the New York Surgical Society Annual Meeting, New York (NY), February 2012.nearly twice as often as males [1]. FNA results in a definitive classification in approximately 70% to 80% of cases, whereas the remaining 20% to 30% of samples are characterized as indeterminate [2, 3]. These lesions show a follicular growth pattern and FNA is not sufficient to distinguish between benign and malignant lesions. Indeterminate FNA lesions present a problem for both the patient and the clinician as at least 20% harbor a malignant diagnosis and require at least a hemithyroidectomy for determining final diagnosis [4]. When the definitive diagnosis is consistent with malignancy, patients typically undergo a second surgical procedure in the form of a completion thyroidectomy.
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