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J Clin Endocrinol Metab. 2015 Jul;100(7):2743-50. doi: 10.1210/jc.2015-1158. Epub 2015 May 12.

Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules With Indeterminate Cytology.

Author information

1
Asuragen, Inc (E.L., B.A., D.W., S.B.H.), Austin, Texas 78744; Jersey Shore University Medical Center (A.S.), Center for Thyroid, Parathyroid and Adrenal Diseases, Neptune, New Jersey 07753; Metropolitan Fine Needle Aspiration Service (A.E.B.), Washington, District of Columbia 20037 and Bethesda, Maryland 20814; Thyroid & Endocrine Center of Florida (M.A.L.), Sarasota, Florida 34231; and (M.L.M.) San Diego, California 92103.

Abstract

CONTEXT:

Molecular testing for oncogenic mutations or gene expression in fine-needle aspirations (FNAs) from thyroid nodules with indeterminate cytology identifies a subset of benign or malignant lesions with high predictive value.

OBJECTIVE:

This study aimed to evaluate a novel diagnostic algorithm combining mutation detection and miRNA expression to improve the diagnostic yield of molecular cytology.

SETTING:

Surgical specimens and preoperative FNAs (n = 638) were tested for 17 validated gene alterations using the miRInform Thyroid test and with a 10-miRNA gene expression classifier generating positive (malignant) or negative (benign) results.

DESIGN:

Cross-sectional sampling of thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) or follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN) cytology (n = 109) was conducted at 12 endocrinology centers across the United States. Qualitative molecular results were compared with surgical histopathology to determine diagnostic performance and model clinical effect.

RESULTS:

Mutations were detected in 69% of nodules with malignant outcome. Among mutation-negative specimens, miRNA testing correctly identified 64% of malignant cases and 98% of benign cases. The diagnostic sensitivity and specificity of the combined algorithm was 89% (95% confidence interval [CI], 73-97%) and 85% (95% CI, 75-92%), respectively. At 32% cancer prevalence, 61% of the molecular results were benign with a negative predictive value of 94% (95% CI, 85-98%). Independently of variations in cancer prevalence, the test increased the yield of true benign results by 65% relative to mRNA-based gene expression classification and decreased the rate of avoidable diagnostic surgeries by 69%.

CONCLUSIONS:

Multiplatform testing for DNA, mRNA, and miRNA can accurately classify benign and malignant thyroid nodules, increase the diagnostic yield of molecular cytology, and further improve the preoperative risk-based management of benign nodules with AUS/FLUS or FN/SFN cytology.

PMID:
25965083
PMCID:
PMC4490308
DOI:
10.1210/jc.2015-1158
[Indexed for MEDLINE]
Free PMC Article
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