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

Xavier M. Keutgen, Filippo Filicori, Michael J. Crowley, Yongchun Wang, Theresa Scognamiglio, Rana Hoda, Daniel Buitrago, David S Cooper, Martha A. Zeiger, Rasa Zarnegar, Olivier Elemento, Thomas J. Fahey

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2032-2038
Number of pages7
JournalClinical Cancer Research
Volume18
Issue number7
DOIs
StatePublished - Apr 1 2012

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Fine Needle Biopsy
MicroRNAs
Thyroid Gland
Oxyphil Cells
Sensitivity and Specificity
Thyroid Nodule
Thyroidectomy
Statistical Models
Reverse Transcriptase Polymerase Chain Reaction
Tertiary Care Centers
Neoplasms
Research Design

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. / Keutgen, Xavier M.; Filicori, Filippo; Crowley, Michael J.; Wang, Yongchun; Scognamiglio, Theresa; Hoda, Rana; Buitrago, Daniel; Cooper, David S; Zeiger, Martha A.; Zarnegar, Rasa; Elemento, Olivier; Fahey, Thomas J.

In: Clinical Cancer Research, Vol. 18, No. 7, 01.04.2012, p. 2032-2038.

Research output: Contribution to journalArticle

Keutgen, XM, Filicori, F, Crowley, MJ, Wang, Y, Scognamiglio, T, Hoda, R, Buitrago, D, Cooper, DS, Zeiger, MA, Zarnegar, R, Elemento, O & Fahey, TJ 2012, 'A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration', Clinical Cancer Research, vol. 18, no. 7, pp. 2032-2038. https://doi.org/10.1158/1078-0432.CCR-11-2487
Keutgen, Xavier M. ; Filicori, Filippo ; Crowley, Michael J. ; Wang, Yongchun ; Scognamiglio, Theresa ; Hoda, Rana ; Buitrago, Daniel ; Cooper, David S ; Zeiger, Martha A. ; Zarnegar, Rasa ; Elemento, Olivier ; Fahey, Thomas J. / A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 7. pp. 2032-2038.
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T1 - A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration

AU - Keutgen, Xavier M.

AU - Filicori, Filippo

AU - Crowley, Michael J.

AU - Wang, Yongchun

AU - Scognamiglio, Theresa

AU - Hoda, Rana

AU - Buitrago, Daniel

AU - Cooper, David S

AU - Zeiger, Martha A.

AU - Zarnegar, Rasa

AU - Elemento, Olivier

AU - Fahey, Thomas J.

PY - 2012/4/1

Y1 - 2012/4/1

N2 - 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.

AB - 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.

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