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

作者：Emmanuel Labourier, Alexander L. Shifrin, Anne E. Busseniers, Mark Armin Lupo, Monique L. Manganelli, Bernard F. Andruss, Dennis Wylie, Sylvie Beaudenon‐Huibregtse · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2015 · DOI：10.1210/jc.2015-1158 · 被引用次数：281 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Thyroid Disorders and Treatments、Thyroid and Parathyroid Surgery

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...