{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:21:57Z","timestamp":1784535717686,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Medullary thyroid carcinoma (MTC) is an aggressive malignancy originating from the parafollicular C cells. Preoperatively, thyroid nodule fine\u2010needle aspiration cytology (FNAC) and pathogenic gene mutations are definitive in approximately one\u2010half of cases. MicroRNAs (miRNAs) are endogenous, noncoding, single\u2010stranded RNAs that regulate gene expression, a characteristic that confers the potential for identifying malignancy. In the current study, the authors hypothesized that differential pairwise (diff\u2010pair) analysis of miRNA expression levels would reliably identify MTC in FNA samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The relative abundance of 10 different miRNAs in total nucleic acids was obtained from ThyraMIR test results. Diff\u2010pair analysis was performed by subtracting the critical threshold value of one miRNA from the critical threshold values of other miRNAs. Next\u2010generation sequencing with the ThyGeNEXT panel identified oncogenic gene alterations. The discovery cohort consisted of 30 formalin\u2010fixed, paraffin\u2010embedded benign and malignant thyroid neoplasms, including 4 cases of MTC. After analytical validation, clinical validation was performed using 3 distinct cohorts (total of 7557 specimens).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the discovery cohort, 9 diff\u2010pairs were identified as having significant power using the Kruskal\u2010Wallis test (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001) to distinguish MTC samples from non\u2010MTC samples. The assay correctly classified all MTC and non\u2010MTC samples in the analytical validation study and in the 3 clinical validation cohorts. The overall test accuracy was 100% (95% confidence interval, 99%\u2010100%). In indeterminate FNAC samples, the sensitivity of the diff\u2010pair analysis was greater than that of the MTC\u2010specific mutation analysis (100% vs 25%; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.03).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pairwise miRNA expression analysis of ThyraMIR results were found to accurately predict MTC in thyroid FNA samples, including those with indeterminate FNAC findings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22365","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T17:29:42Z","timestamp":1601918982000},"page":"239-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Analytical and clinical validation of pairwise microRNA expression analysis to identify medullary thyroid cancer in thyroid fine\u2010needle aspiration samples"],"prefix":"10.1002","volume":"129","author":[{"given":"Andrea 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