{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T10:06:46Z","timestamp":1779012406058,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Indeterminate thyroid nodules carry a wide range of malignancy prevalence, necessitating\u00a0incorporation of molecular testing to guide management. Molecular test results help guide prognosis to a certain extent, but additional prognostic factors need to be identified. Limited data have linked\n                    <jats:italic>PLEKHS1<\/jats:italic>\n                    promoter (\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    ) mutations with higher aggressiveness of thyroid cancer. Hence, we aimed to evaluate the diagnostic and prognostic value of\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations in preoperative thyroid nodules undergoing molecular testing. We assessed\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations in 9279 patient samples from April 2023 to June 2024 among indeterminate thyroid nodules ((B)ethesda III\/IV) with Afirma GSC\u2010(S)uspicious results as well as among B V\/VI cytology thyroid nodules. We also analyzed a subset of 20 consecutive cases positive for\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations with surgical resection for histology and for co\u2010occurring molecular alterations from the Afirma testing.\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations were positive in 60\/9279 (0.6%) of patient samples with three times higher frequency in B VI compared to B III cytology nodules (1.36% vs 0.47%,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a0.01). Among the 60 samples harboring\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations, 28 had the C593T hotspot mutation, 38 the G590A mutation, and six samples had both; four samples had concomitant\n                    <jats:italic>TERTp<\/jats:italic>\n                    mutations and 18 samples had concomitant\n                    <jats:italic>BRAFp.V600E<\/jats:italic>\n                    alterations. Our study demonstrated an overall low frequency of\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations, but this frequency was highest among malignant (B VI) cytology thyroid nodules. The frequency of\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations did not strongly correlate with the severity of thyroid cancer but the surgical sample size was limited. Further research is needed to clarify the role of\n                    <jats:italic>PLEKHS1p<\/jats:italic>\n                    mutations in thyroid nodules and cancer.\n                  <\/jats:p>","DOI":"10.1002\/cncy.70103","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:18:06Z","timestamp":1777900686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of\n                    <i>PLEKHS1<\/i>\n                    promoter mutation in preoperative thyroid nodule samples"],"prefix":"10.1002","volume":"134","author":[{"given":"Sarah","family":"Azad","sequence":"first","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy E.","family":"Graham","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Endocrine Treatment Specialists  Sandy Utah USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiri","family":"Levy","sequence":"additional","affiliation":[{"name":"Henry Ford Health  Detroit Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evana","family":"Velanzuela\u2010Sheker","sequence":"additional","affiliation":[{"name":"Memorial Healthcare System  Hollywood Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bimston","sequence":"additional","affiliation":[{"name":"Memorial Healthcare System  Hollywood Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Ferenczi","sequence":"additional","affiliation":[{"name":"Endocrinology Associates, P.A.  Scottsdale Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Veracyte, Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Alshalalfa","sequence":"additional","affiliation":[{"name":"Veracyte, Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Hao","sequence":"additional","affiliation":[{"name":"Veracyte, Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua P.","family":"Klopper","sequence":"additional","affiliation":[{"name":"Veracyte, Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-7387","authenticated-orcid":false,"given":"Richard T.","family":"Kloos","sequence":"additional","affiliation":[{"name":"Veracyte, Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4500-8546","authenticated-orcid":false,"given":"Anupam","family":"Kotwal","sequence":"additional","affiliation":[{"name":"Division of Diabetes, Endocrinology, and Metabolism University of Nebraska Medical Center  Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.2719"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2023.0141"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1101410"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.09.050"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013\u20103734"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3101"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.10706"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12082133"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0459"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2025.109698"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae134"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22744"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00612"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab304"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad220"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201018\u20102953"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.70103","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncy.70103","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.70103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T09:17:27Z","timestamp":1779009447000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.70103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/cncy.70103"],"URL":"https:\/\/doi.org\/10.1002\/cncy.70103","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"value":"1934-662X","type":"print"},{"value":"1934-6638","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70103"}}