{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:17:21Z","timestamp":1784837841600,"version":"3.55.0"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Loss of thyroid differentiation underlies the aggressive behavior of a subset of papillary thyroid carcinomas (PTCs). The Thyroid Differentiation Score (TDS), introduced by The Cancer Genome Atlas (TCGA), quantifies tumor differentiation but has limited reproducibility and clinical applicability. We developed and validated a revised score (xTDS) that enables reproducible assessment of tumor differentiation with prognostic relevance across cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed RNA sequencing data from 570 patients with PTC across three independent cohorts: a discovery cohort from the MD Anderson Cancer Center (n = 111) and two external validation cohorts from Vanderbilt University (n = 69) and TCGA (n = 390). xTDS was evaluated for correlation with the original TDS, association with oncogenic drivers, and prognostic value for disease-specific survival (DSS) and progression-free survival (PFS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      xTDS showed near-perfect correlation with the original TDS (Spearman \u03c1 = 0.98) and recapitulated known biological patterns, with\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      V600E\u2013driven tumors exhibiting the lowest differentiation scores and\n                      <jats:italic toggle=\"yes\">RAS<\/jats:italic>\n                      -driven tumors the highest across all cohorts (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). Low xTDS was associated with worse DSS in the MD Anderson (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) and Vanderbilt (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .005) cohorts and showed a similar numerical trend in TCGA, without statistical significance because of limited events. Low xTDS was consistently associated with worse PFS across all three cohorts (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .048, &lt;0.001, and 0.007, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>xTDS is a reproducible measure of thyroid differentiation that preserves the biological and prognostic relevance of the original TDS while overcoming technical constraints affecting reproducibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-26-00207","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T19:59:23Z","timestamp":1784836763000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Revised Thyroid Differentiation Score for Risk Stratification in Papillary Thyroid Carcinoma"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7005-722X","authenticated-orcid":true,"given":"Vicente R.","family":"Marczyk","sequence":"first","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-6016","authenticated-orcid":true,"given":"Chia Chin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-9885","authenticated-orcid":true,"given":"Sarah","family":"Hamidi","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-9906","authenticated-orcid":true,"given":"Sophie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-4591","authenticated-orcid":true,"given":"Matthew A.","family":"Loberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0911-6381","authenticated-orcid":true,"given":"Meghan","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9133-7332","authenticated-orcid":true,"given":"Michelle D.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3626-9928","authenticated-orcid":true,"given":"Sayed Mohsen","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0280-0100","authenticated-orcid":true,"given":"Steven","family":"Waguespack","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-030X","authenticated-orcid":true,"given":"Mimi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-5153","authenticated-orcid":true,"given":"Steven I.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-7286","authenticated-orcid":true,"given":"Stephen","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-2539","authenticated-orcid":true,"given":"Yaoyi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0617-9438","authenticated-orcid":true,"given":"Wenyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX"},{"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4354-2841","authenticated-orcid":true,"given":"Anastasios","family":"Maniakas","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7918-9739","authenticated-orcid":true,"given":"Mark","family":"Zafereo","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-9295","authenticated-orcid":true,"given":"Quanhu","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2129-5701","authenticated-orcid":true,"given":"George J.","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8745-0025","authenticated-orcid":true,"given":"Eric C.","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-3207","authenticated-orcid":true,"given":"Vivian L.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, 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