Labourier Emmanuel, Shifrin Alexander, Busseniers Anne E, Lupo Mark A, Manganelli Monique L, Andruss Bernard, Wylie Dennis, Beaudenon-Huibregtse Sylvie
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.
J Clin Endocrinol Metab. 2015 Jul;100(7):2743-50. doi: 10.1210/jc.2015-1158. Epub 2015 May 12.
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.
This study aimed to evaluate a novel diagnostic algorithm combining mutation detection and miRNA expression to improve the diagnostic yield of molecular cytology.
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.
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.
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%.
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.
对甲状腺结节细针穿刺（FNA）进行致癌基因突变或基因表达的分子检测，可识别出具有高预测价值的良性或恶性病变子集。
本研究旨在评估一种结合突变检测和miRNA表达的新型诊断算法，以提高分子细胞学的诊断率。
使用miRInform甲状腺检测和10-miRNA基因表达分类器对手术标本和术前FNA（n = 638）进行17种已验证的基因改变检测，得出阳性（恶性）或阴性（良性）结果。
在美国12个内分泌中心对具有意义不明确的非典型性/意义不明确的滤泡性病变（AUS/FLUS）或滤泡性肿瘤/疑似滤泡性肿瘤（FN/SFN）细胞学的甲状腺结节（n = 109）进行横断面抽样。将定性分子结果与手术组织病理学进行比较，以确定诊断性能并模拟临床效果。
在具有恶性结果的结节中，69%检测到突变。在突变阴性标本中，miRNA检测正确识别出64%的恶性病例和98%的良性病例。联合算法的诊断敏感性和特异性分别为89%（95%置信区间[CI]，73 - 97%）和85%（95%CI，75 - 92%）。在癌症患病率为32%时，61%的分子结果为良性，阴性预测值为94%（95%CI，85 - 98%）。与基于mRNA的基因表达分类相比，该检测方法与癌症患病率的变化无关，将真正良性结果的检出率提高了65%，并将可避免的诊断性手术率降低了69%。
对DNA、mRNA和miRNA进行多平台检测可准确分类良性和恶性甲状腺结节，提高分子细胞学的诊断率，并进一步改善对具有AUS/FLUS或FN/SFN细胞学的良性结节基于术前风险的管理。
