{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:11:15Z","timestamp":1777500675933,"version":"3.51.4"},"reference-count":22,"publisher":"BMJ","issue":"11","funder":[{"name":"Institute of Molecular and Cellular Biology","award":["0310-2019-0013"],"award-info":[{"award-number":["0310-2019-0013"]}]},{"DOI":"10.13039\/501100024490","name":"Institute of Cytology and Genetics","doi-asserted-by":"crossref","award":["0324-2019-0040-C-01"],"award-info":[{"award-number":["0324-2019-0040-C-01"]}],"id":[{"id":"10.13039\/501100024490","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2020,3,1]]},"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Analysis of molecular markers in addition to cytological analysis of fine-needle aspiration (FNA) samples is a promising way to improve the preoperative diagnosis of thyroid nodules. Previously, we have developed an algorithm for the differential diagnosis of thyroid nodules by means of a small set of molecular markers. Here, we aimed to validate this approach using FNA cytology samples of Bethesda categories III and IV, in which preoperative detection of malignancy by cytological analysis is impossible.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 122 FNA smears from patients with indeterminate cytology (Bethesda III: 13 patients, Bethesda IV: 109 patients) were analysed by real-time PCR regarding the preselected set of molecular markers (the\n                      <jats:italic>BRAF<\/jats:italic>\n                      V600E mutation, normalised concentrations of\n                      <jats:italic>HMGA2<\/jats:italic>\n                      mRNA, 3 microRNAs, and the mitochondrial\/nuclear DNA ratio). The decision tree\u2013based classifier was used to discriminate between benign and malignant tumours.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The molecular testing detected malignancy in FNA smears of indeterminate cytology with 89.2% sensitivity, 84.6% positive predictive value, 92.9% specificity and 95.2% negative predictive value; these characteristics are comparable with those of more complicated commercial tests. Residual risk of malignancy for the thyroid nodules that were shown to be benign by this molecular method did not exceed the reported risk of malignancy for Bethesda II histological diagnosis. Analytical-accuracy assessment revealed required nucleic-acid input of \u22655\u2009ng.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study shows feasibility of preoperative differential diagnosis of thyroid nodules of indeterminate cytology using a small panel of molecular markers of different types by a simple PCR-based method using stained FNA smears.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jclinpath-2020-206445","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T17:15:33Z","timestamp":1585156533000},"page":"722-727","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier"],"prefix":"10.1136","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9401-5737","authenticated-orcid":false,"given":"Sergei","family":"Titov","sequence":"first","affiliation":[{"name":"Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology SB RAS, Novosibirsk, Russian Federation"},{"name":"AO Vector-Best, Novosibirsk, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9433-8341","authenticated-orcid":false,"given":"Pavel S","family":"Demenkov","sequence":"additional","affiliation":[{"name":"Department of Systems Biology, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russian Federation"},{"name":"Department of Mathematics and Mechanics, Novosibirsk State University, Novosibirsk, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei A","family":"Lukyanov","sequence":"additional","affiliation":[{"name":"Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei V","family":"Sergiyko","sequence":"additional","affiliation":[{"name":"Department of General and Pediatric Surgery, South Ural State Medical University, Chelyabinsk, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gevork A","family":"Katanyan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Regional Clinical Hospital No. 2, Krasnodar, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia A","family":"Veryaskina","sequence":"additional","affiliation":[{"name":"Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology SB RAS, Novosibirsk, Russian Federation"},{"name":"Department of Systems Biology, Institute of Cytology and Genetics SB RAS, Novosibirsk, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail K","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Department of the Structure and Function of Chromosomes, Institute of Molecular and Cellular Biology SB RAS, Novosibirsk, Russian Federation"},{"name":"AO Vector-Best, Novosibirsk, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"2025112108532246000_73.11.722.1","doi-asserted-by":"publisher","DOI":"10.1159\/000339959"},{"key":"2025112108532246000_73.11.722.2","doi-asserted-by":"publisher","DOI":"10.1002\/dc.20830"},{"key":"2025112108532246000_73.11.722.3","doi-asserted-by":"crossref","unstructured":"Ali S , Cibas E . 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