{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:00:04Z","timestamp":1780635604737,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T00:00:00Z","timestamp":1780099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Risk stratification of thyroid nodules is mainly based on ultrasound examination and fine-needle aspiration (FNA) cytology findings. Molecular testing has increasingly been added to the workup to improve risk of malignancy (ROM) estimation. Here, we evaluated the diagnostic performance of alterations in seven genes, including point mutations in BRAF, HRAS, KRAS, and NRAS as well as RET\/PTC1, RET\/PTC3, and PAX8\/PPAR\u03b3 fusions in 849 FNA samples with cytopathologically indeterminate Bethesda categories (III, IV, and V). In 20.14% of samples, at least one gene alteration was detected, with NRAS mutations and the BRAF V600E variant occurring most frequently. For 636 of the thyroid nodules, surgical follow-up was available, with a malignancy rate of 22.64%. BRAF V600E mutations and RET\/PTC1 fusions were associated with a ROM of 100%, RAS mutations with 13.64%, and PAX8\/PPAR\u03b3 fusions with 60.00%. Depending on the Bethesda category, the positive predictive value for malignancy of the seven-gene panel ranged between 18.18% (Bethesda III) and 91.07% (Bethesda V), while the negative predictive value ranged between 93.92% (Bethesda III) and 24.14% (Bethesda V). In conclusion, molecular testing with the seven-gene panel can improve ROM estimation in cytopathologically indeterminate thyroid nodules, but its clinical utility depends on the detected gene alteration.<\/jats:p>","DOI":"10.3390\/ijms27114990","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4990","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Performance of Seven-Gene Panel Testing for Risk Stratification of Thyroid Nodules with Indeterminate Cytology Results"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-1384","authenticated-orcid":false,"given":"Ann-Kristin","family":"Jochum","sequence":"first","affiliation":[{"name":"Institute of Pathology, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"},{"name":"Institute of Pathology, Stadtspital Z\u00fcrich, 8063 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6053-298X","authenticated-orcid":false,"given":"Frida","family":"Renstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2844-1601","authenticated-orcid":false,"given":"Barbara","family":"Bischofberger-Baumann","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izadora","family":"Demmer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Sch\u00f6negg","sequence":"additional","affiliation":[{"name":"Institute of Pathology, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Br\u00e4ndle","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Bilz","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-2020","authenticated-orcid":false,"given":"Wolfram","family":"Jochum","sequence":"additional","affiliation":[{"name":"Institute of Pathology, HOCH Health Ostschweiz, 9007 St. Gallen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1089\/thy.2016.0100","article-title":"Systematic Review of Trends in the Incidence Rates of Thyroid Cancer","volume":"26","author":"Wiltshire","year":"2016","journal-title":"Thyroid"},{"key":"ref_2","unstructured":"NICER (2026, February 07). 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