{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:46:07Z","timestamp":1765889167758,"version":"build-2065373602"},"reference-count":70,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T00:00:00Z","timestamp":1693094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"publisher","award":["503\/1-153-05\/503-11-001"],"award-info":[{"award-number":["503\/1-153-05\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The aim of the study was to analyze the diagnostic usefulness of the combined assessment of the ultrasound risk category of the nodule (evaluated with EU-TIRADS system), the presence of BRAF V600E mutation and the expression of selected microRNAs (miR-146b, miR-221 and miR-222) in Bethesda category III thyroid nodules, separately for cases with nuclear atypia (AUS-nuclear) and cases with other types of atypia (AUS-other). We evaluated 161 nodules (66 AUS-nuclear and 95 AUS-other) with known results of postoperative histopathological examination. The rate of cancer and the rate of PTC among cancers were nearly three times higher in the AUS-nuclear than the AUS-other group. For AUS-nuclear nodules, the most effective diagnostic panel included, in addition to repeat FNA, the assessment of BRAF V600E mutation and the expression of miR-146b and miR-222 (sensitivity: 93.5%, specificity: 80.0%). For AUS-other nodules, a two-step procedure was most effective: at the first stage, forgoing surgical treatment in subjects with a benign repeat FNA outcome, and, at the second stage, the assessment of miR-222 expression and the EU-TIRADS category (sensitivity: 92.3%, specificity: 76.8%). The optimal use of molecular methods in the diagnostics of category III thyroid nodules requires a separate approach for nodules with nuclear atypia and nodules with other types of atypia.<\/jats:p>","DOI":"10.3390\/cancers15174287","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T05:46:47Z","timestamp":1693201607000},"page":"4287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effective Use of microRNA, BRAF and Sonographic Risk Assessment in Bethesda III Thyroid Nodules Requires a Different Approach to Nodules with Features of Nuclear Atypia and Other Types of Atypia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5617-0418","authenticated-orcid":false,"given":"Dorota","family":"S\u0142owi\u0144ska-Klencka","sequence":"first","affiliation":[{"name":"Department of Morphometry of Endocrine Glands, Medical University of Lodz, Pomorska 251 St., 92-213 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9943-660X","authenticated-orcid":false,"given":"Bo\u017cena","family":"Popowicz","sequence":"additional","affiliation":[{"name":"Department of Morphometry of Endocrine Glands, Medical University of Lodz, Pomorska 251 St., 92-213 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2875-1995","authenticated-orcid":false,"given":"Dominika","family":"Kulczycka-Wojdala","sequence":"additional","affiliation":[{"name":"Research Laboratory CoreLab, Medical University of Lodz, Mazowiecka 6\/8 St., 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-7570","authenticated-orcid":false,"given":"Bo\u017cena","family":"Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Research Laboratory CoreLab, Medical University of Lodz, Mazowiecka 6\/8 St., 92-215 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-192X","authenticated-orcid":false,"given":"Joanna","family":"Duda-Szyma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Medical University of Lodz, Pomorska 251 St., 92-213 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6339-1323","authenticated-orcid":false,"given":"Martyna","family":"Wojtaszek-Nowicka","sequence":"additional","affiliation":[{"name":"Department of Clinical Endocrinology, Medical University of Lodz, Pomorska 251 St., 92-213 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-0979","authenticated-orcid":false,"given":"Krzysztof","family":"Kaczka","sequence":"additional","affiliation":[{"name":"Department of General and Oncological Surgery, Surgical Clinical Sciences, Medical University of Lodz, Pomorska 251 St., 92-213 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-0897","authenticated-orcid":false,"given":"Mariusz","family":"Klencki","sequence":"additional","affiliation":[{"name":"Department of Morphometry of Endocrine Glands, Medical University of Lodz, Pomorska 251 St., 92-213 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000478927","article-title":"European Thyroid Association Guidelines for Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS","volume":"6","author":"Russ","year":"2017","journal-title":"Eur. Thyroid J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1309\/AJCPPHLWMI3JV4LA","article-title":"NCI Thyroid FNA State of the Science Conference. The Bethesda System for Reporting Thyroid Cytopathology","volume":"132","author":"Cibas","year":"2009","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1089\/thy.2017.0500","article-title":"The 2017 Bethesda System for Reporting Thyroid Cytopathology","volume":"27","author":"Cibas","year":"2017","journal-title":"Thyroid"},{"doi-asserted-by":"crossref","unstructured":"Ali, S.Z., Baloch, Z.W., Cochand-Priollet, B., Schmitt, F.C., Vielh, P., and VanderLaan, P.A. (2023). The 2023 Bethesda System for reporting thyroid cytopathology. J. Am. Soc. Cytopathol., in press.","key":"ref_5","DOI":"10.1089\/thy.2023.0141"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3913","DOI":"10.1245\/s10434-018-6826-6","article-title":"Both Ultrasound Features and Nuclear Atypia are Associated with Malignancy in Thyroid Nodules with Atypia of Undetermined Significance","volume":"25","author":"Eisa","year":"2018","journal-title":"Ann. Surg. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/cncy.22228","article-title":"Differences in surgical resection rate and risk of malignancy in thyroid cytopathology practice between Western and Asian countries: A systematic review and meta-analysis","volume":"128","author":"Vuong","year":"2020","journal-title":"Cancer Cytopathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4103\/1742-6413.139725","article-title":"Diagnosis of atypia\/follicular lesion of undetermined significance: An institutional experience","volume":"11","author":"Wong","year":"2014","journal-title":"Cytojournal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/cncy.21412","article-title":"Should the thyroid AUS\/FLUS category be further stratified by malignancy risk?","volume":"122","author":"Nishino","year":"2014","journal-title":"Cancer Cytopathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/cyt.12352","article-title":"Risk of malignancy according to sub-classification of the atypia of undetermined significance or follicular lesion of undetermined significance (AUS\/FLUS) category in the Bethesda system for reporting thyroid cytopathology","volume":"28","author":"Kim","year":"2017","journal-title":"Cytopathology"},{"doi-asserted-by":"crossref","unstructured":"S\u0142owi\u0144ska-Klencka, D., Klencki, M., Duda-Szyma\u0144ska, J., and Popowicz, B. (2022). Optimization of the Management of Category III Thyroid Nodules Using Repeat FNA and TIRADS. Cancers, 14.","key":"ref_11","DOI":"10.3390\/cancers14184489"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12022-022-09707-3","article-title":"Overview of the 2022 WHO Classification of Thyroid Neoplasms","volume":"33","author":"Baloch","year":"2022","journal-title":"Endocr. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12020-019-02184-5","article-title":"Sonographic features of follicular variant of papillary thyroid carcinoma (FV-PTC) and diagnostic performance of the 2017 ACR TI-RADS in FV-PTC","volume":"67","author":"Zhang","year":"2020","journal-title":"Endocrine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3803\/EnM.2015.30.3.252","article-title":"Mutation Profile of Well-Differentiated Thyroid Cancer in Asians","volume":"30","author":"Song","year":"2015","journal-title":"Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/dc.24522","article-title":"Molecular testing in diagnosis of indeterminate thyroid cytology: Trends and drivers","volume":"48","author":"Kumar","year":"2020","journal-title":"Diagn. Cytopathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12022-020-09643-0","article-title":"Impact of Molecular Testing on the Management of Indeterminate Thyroid Nodules Among Western and Asian Countries: A Systematic Review and Meta-analysis","volume":"32","author":"Ngo","year":"2021","journal-title":"Endocr. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1210\/jc.2015-1158","article-title":"Molecular Testing for miRNA, mRNA, and DNA on Fine-Needle Aspiration Improves the Preoperative Diagnosis of Thyroid Nodules with Indeterminate Cytology","volume":"100","author":"Labourier","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1136\/jclinpath-2020-206445","article-title":"Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier","volume":"73","author":"Titov","year":"2020","journal-title":"J. Clin. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1089\/thy.2015.0305","article-title":"Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance\/Follicular Lesion of Undetermined Significance Cytology","volume":"25","author":"Nikiforov","year":"2015","journal-title":"Thyroid"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1056\/NEJMoa1203208","article-title":"Preoperative diagnosis of benign thyroid nodules with indeterminate cytology","volume":"367","author":"Alexander","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/cjp2.38","article-title":"Molecular classification of thyroid lesions by combined testing for miRNA gene expression and somatic gene alterations","volume":"2","author":"Wylie","year":"2016","journal-title":"J. Pathol. Clin. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R163","DOI":"10.1530\/ERC-17-0405","article-title":"Genetic testing for indeterminate thyroid cytology: Review and meta-analysis","volume":"25","author":"Urra","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/dc.24087","article-title":"The utility of combined mutation analysis and microRNA classification in reclassifying cancer risk of cytologically indeterminate thyroid nodules","volume":"47","author":"Banizs","year":"2019","journal-title":"Diagn. Cytopathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1002\/dc.24564","article-title":"Multiplatform molecular test performance in indeterminate thyroid nodules","volume":"48","author":"Lupo","year":"2020","journal-title":"Diagn. Cytopathol."},{"doi-asserted-by":"crossref","unstructured":"Rogucki, M., Buczy\u0144ska, A., Kr\u0119towski, A.J., and Pop\u0142awska-Kita, A. (2021). The Importance of miRNA in the Diagnosis and Prognosis of Papillary Thyroid Cancer. J. Clin. Med., 10.","key":"ref_25","DOI":"10.3390\/jcm10204738"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jasc.2017.02.001","article-title":"The role of miRNAs in the evaluation of follicular thyroid neoplasms: An overview of literature","volume":"6","author":"Rossi","year":"2017","journal-title":"J. Am. Soc. Cytopathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2052396","DOI":"10.1155\/2020\/2052396","article-title":"Differential MicroRNA-Signatures in Thyroid Cancer Subtypes","volume":"2020","author":"Santiago","year":"2020","journal-title":"J. Oncol."},{"key":"ref_28","first-page":"6496570","article-title":"MicroRNAs as Biomarkers in Thyroid Carcinoma","volume":"2017","author":"Celano","year":"2017","journal-title":"Int. J. Genom."},{"doi-asserted-by":"crossref","unstructured":"S\u0142owi\u0144ska-Klencka, D., Wysocka-Konieczna, K., Klencki, M., and Popowicz, B. (2020). Diagnostic Value of Six Thyroid Imaging Reporting and Data Systems (TIRADS) in Cytologically Equivocal Thyroid Nodules. J. Clin. Med., 9.","key":"ref_29","DOI":"10.3390\/jcm9072281"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/cncy.22235","article-title":"Can ultrasound systems for risk stratification of thyroid nodules identify follicular carcinoma?","volume":"128","author":"Castellana","year":"2020","journal-title":"Cancer Cytopathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"794490","DOI":"10.3389\/fendo.2021.794490","article-title":"Biomarker Value of miR-221 and miR-222 as Potential Substrates in the Differential Diagnosis of Papillary Thyroid Cancer Based on Data Synthesis and Bioinformatics Approach","volume":"12","author":"Cai","year":"2022","journal-title":"Front. Endocrinol."},{"doi-asserted-by":"crossref","unstructured":"Chou, C.K., Liu, R.T., and Kang, H.Y. (2017). MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer. Int. J. Mol. Sci., 18.","key":"ref_32","DOI":"10.3390\/ijms18030636"},{"unstructured":"Lloyd, R., Osamura, R., Kloppel, G., and Rosai, J. (2017). WHO Classification of Tumours of Endocrine Organs.","key":"ref_33"},{"unstructured":"WHO (2023, April 07). WHO Classification of Tumours Editorial Board: Endocrine and Neuroendocrine Tumours, Available online: https:\/\/tumourclassification.iarc.who.int.","key":"ref_34"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1089\/thy.2020.0969","article-title":"Repeat Fine Needle Aspiration Cytology Refines the Selection of Thyroid Nodules for Afirma Gene Expression Classifier Testing","volume":"31","author":"Nishino","year":"2021","journal-title":"Thyroid"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.ejso.2016.11.003","article-title":"BRAFV600E mutation as a predictor of thyroid malignancy in indeterminate nodules: A systematic review and meta-analysis","volume":"43","author":"Jinih","year":"2017","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/modpathol.2016.157","article-title":"miRNA expression profiling of \u2018noninvasive follicular thyroid neoplasms with papillary-like nuclear features\u2019 compared with adenomas and infiltrative follicular variants of papillary thyroid carcinomas","volume":"30","author":"Borrelli","year":"2017","journal-title":"Mod. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1159\/000528860","article-title":"Thyroid fine needle aspiration, the Bethesda System and the BRAFV600E mutation in Papillary Thyroid Carcinoma. Association and prediction for biopsy","volume":"67","year":"2023","journal-title":"Acta Cytol."},{"doi-asserted-by":"crossref","unstructured":"Lewi\u0144ski, A., Adamczewski, Z., Zygmunt, A., Markuszewski, L., Karbownik-Lewi\u0144ska, M., and Stasiak, M. (2019). Correlations between Molecular Landscape and Sonographic Image of Different Variants of Papillary Thyroid Carcinoma. J. Clin. Med., 8.","key":"ref_39","DOI":"10.3390\/jcm8111916"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.21037\/gs-20-430","article-title":"Prevalence of BRAFV600E mutation in Asian series of papillary thyroid carcinoma-a contemporary systematic review","volume":"9","author":"Rashid","year":"2020","journal-title":"Gland. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1530\/EJE-12-0993","article-title":"Low malignancy risk of thyroid follicular lesion of undetermined significance in patients from post-endemic areas","volume":"168","author":"Wojtaszek","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/cen.12806","article-title":"BRAF-mutated carcinomas among thyroid nodules with prior indeterminate FNA report: A systematic review and meta-analysis","volume":"84","author":"Trimboli","year":"2016","journal-title":"Clin. Endocrinol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s12020-021-02693-2","article-title":"Real-life use of BRAF-V600E mutation analysis in thyroid nodule fine needle aspiration: Consequences on clinical decision-making","volume":"73","author":"Brigante","year":"2021","journal-title":"Endocrine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1530\/EJE-12-0400","article-title":"MicroRNA expression profile helps to distinguish benign nodules from papillary thyroid carcinomas starting from cells of fine-needle aspiration","volume":"167","author":"Agretti","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.5603\/EP.2016.0006","article-title":"The usefulness of determining the presence of BRAF V600E mutation in fine-needle aspiration cytology in indeterminate cytological results","volume":"67","author":"Kowalska","year":"2016","journal-title":"Endokrynol. Pol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1016\/j.humpath.2015.06.001","article-title":"Diagnostic value of fine needle aspiration BRAF(V600E) mutation analysis in papillary thyroid cancer: A systematic review and meta-analysis","volume":"46","author":"Fnais","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.21037\/gs-20-535","article-title":"BRAFV600E mutation combined with American College of Radiology thyroid imaging report and data system significantly changes surgical resection rate and risk of malignancy in thyroid cytopathology practice","volume":"9","author":"Zhu","year":"2020","journal-title":"Gland. Surg."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5934","DOI":"10.1038\/s41598-022-09822-5","article-title":"Diagnostic value of thyroid imaging reporting and data system combined with BRAFV600E mutation analysis in Bethesda categories III-V thyroid nodules","volume":"12","author":"Wu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/sj.bjc.6605493","article-title":"Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours","volume":"102","author":"Sheu","year":"2010","journal-title":"Br. J. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"128735","DOI":"10.1155\/2013\/128735","article-title":"Expression of miRNAs in Papillary Thyroid Carcinomas Is Associated with BRAF Mutation and Clinicopathological Features in Chinese Patients","volume":"2013","author":"Sun","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1089\/thy.2009.0027","article-title":"miR-146b is highly expressed in adult papillary thyroid carcinomas with high risk features including extrathyroidal invasion and the BRAF(V600E) mutation","volume":"20","author":"Chou","year":"2010","journal-title":"Thyroid"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1427042","DOI":"10.1155\/2016\/1427042","article-title":"Differences in miRNA and mRNA Profile of Papillary Thyroid Cancer Variants","volume":"2016","author":"Stokowy","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_53","first-page":"1144","article-title":"Assessing Bias and Limitations of Clinical Validation Studies of Molecular Diagnostic Tests for Indeterminate Thyroid Nodules: Systematic Review and Meta-Analysis","volume":"32","author":"DiGennaro","year":"2022","journal-title":"Thyroid"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s12020-021-02781-3","article-title":"Low reproducibility of equivocal categories of the Bethesda System for Reporting Thyroid Cytology makes the associated risk of malignancy specific to the diagnostic center","volume":"74","author":"Klencki","year":"2021","journal-title":"Endocrine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1007\/s00268-013-2330-0","article-title":"Utilization and impact of repeat biopsy for follicular lesion\/atypia of undetermined significance","volume":"38","author":"Broome","year":"2014","journal-title":"World J. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/cncy.21468","article-title":"The impact of atypia\/follicular lesion of undetermined significance and repeat fine-needle aspiration: 5 years before and after implementation of the Bethesda System","volume":"122","author":"Sullivan","year":"2014","journal-title":"Cancer Cytopathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1309\/AJCP4P2GCCDNHFMY","article-title":"Clinical outcome for atypia of undetermined significance in thyroid fine-needle aspirations: Should repeated FNA be the preferred initial approach?","volume":"135","author":"VanderLaan","year":"2011","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1210\/jc.2007-2696","article-title":"MicroRNA expression profiling of thyroid tumors: Biological significance and diagnostic utility","volume":"93","author":"Nikiforova","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1038\/modpathol.2008.105","article-title":"MicroRNA analysis as a potential diagnostic tool for papillary thyroid carcinoma","volume":"21","author":"Chen","year":"2008","journal-title":"Mod. Pathol."},{"doi-asserted-by":"crossref","unstructured":"Laukien\u0117, R., Ambrozaityte, L., Cimbalistien\u0117, L., Utkus, A., and Tamosiunas, A.E. (2022). Diagnostic Significance of FNAB miRNA Expression in Papillary Thyroid Carcinoma. Diagnostics, 12.","key":"ref_60","DOI":"10.3390\/diagnostics12061384"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1158\/1078-0432.CCR-11-2487","article-title":"A panel of four miRNAs accurately differentiates malignant from benign indeterminate thyroid lesions on fine needle aspiration","volume":"18","author":"Keutgen","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s40618-018-0880-6","article-title":"MicroRNA expression profile of thyroid nodules in fine-needle aspiration cytology: A confirmatory series","volume":"42","author":"Castagna","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1089\/thy.2011.0313","article-title":"Evaluation of candidate diagnostic microRNAs in thyroid fine-needle aspiration biopsy samples","volume":"22","author":"Kitano","year":"2012","journal-title":"Thyroid"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1089\/thy.2018.0254","article-title":"Molecular Classification of Thyroid Nodules with Indeterminate Cytology: Development and Validation of a Highly Sensitive and Specific New miRNA-Based Classifier Test Using Fine-Needle Aspiration Smear Slides","volume":"28","author":"Santos","year":"2018","journal-title":"Thyroid"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"104137","DOI":"10.1016\/j.ebiom.2022.104137","article-title":"Clinical decision support analysis of a microRNA-based thyroid molecular classifier: A real-world, prospective and multicentre validation study","volume":"82","author":"Santos","year":"2022","journal-title":"EBioMedicine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1089\/thy.2011.0081","article-title":"MicroRNA signature in thyroid fine needle aspiration cytology applied to \u201catypia of undetermined significance\u201d cases","volume":"22","author":"Shen","year":"2012","journal-title":"Thyroid"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1158\/1055-9965.EPI-18-0055","article-title":"Next-Generation Sequencing Identifies a Highly Accurate miRNA Panel That Distinguishes Well-Differentiated Thyroid Cancer from Benign Thyroid Nodules","volume":"27","author":"Mazeh","year":"2018","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/cncy.21554","article-title":"Malignant risk stratification of thyroid FNA specimens with indeterminate cytology based on molecular testing","volume":"123","author":"Savin","year":"2015","journal-title":"Cancer Cytopathol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1007\/s12020-016-1021-7","article-title":"Two-miRNA classifiers differentiate mutation-negative follicular thyroid carcinomas and follicular thyroid adenomas in fine needle aspirations with high specificity","volume":"54","author":"Stokowy","year":"2016","journal-title":"Endocrine"},{"doi-asserted-by":"crossref","unstructured":"Panebianco, F., Mazzanti, C., Tomei, S., Aretini, P., Franceschi, S., Lessi, F., Di Coscio, G., Bevilacqua, G., and Marchetti, I. (2015). The combination of four molecular markers improves thyroid cancer cytologic diagnosis and patient management. BMC Cancer, 15.","key":"ref_70","DOI":"10.1186\/s12885-015-1917-2"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:40:00Z","timestamp":1760128800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/17\/4287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,27]]},"references-count":70,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["cancers15174287"],"URL":"https:\/\/doi.org\/10.3390\/cancers15174287","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2023,8,27]]}}}