{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:42:17Z","timestamp":1793407337456,"version":"4.5.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460469"],"award-info":[{"award-number":["82460469"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2022AAC03559"],"award-info":[{"award-number":["2022AAC03559"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>WHO 2022 classification underscores lineage-defining transcription factors (TFs) as key determinants of pituitary neuroendocrine tumour (PitNET) biology. We hypothesise that interaction between lineage \u201cdriver\u201d (TFs) and proliferative \u201cengine\u201d (Ki-67) provides superior prognostic power for predicting\u00a0recurrence compared to either factor in isolation or to traditional clinicopathological parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>This retrospective cohort study analysed 302 patients who underwent primary Endoscopic Endonasal Transsphenoidal Surgery for PitNETs. Five prognostic models were constructed to simulate diverse pathology laboratory capabilities for global utility: specific TF\/Ki-67 combinations (Model A), specific TFs only (B), unspecific TF multiplicity\/Ki-67 (C), unspecific TF multiplicity only (D), and Ki-67 alone (E). Multivariate Cox regression, adjusted for key clinical confounders, assessed associations with recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-one patients (26.82%) experienced recurrence, median follow-up: 30 months (range: 2\u201369). Model A &amp;amp; C demonstrated superior prognostic performance, identifying multiple high-risk profiles (adjusted HR [adj.HR] range: 5.36-17.70, all P&amp;lt;0.05). The practical Model C performed nearly equivalently to the granular Model A. Their findings were synthesised into simplified 4-tiered molecular risk stratification. Using Tier I as reference, adj.HR for recurrence escalated significantly across tiers: Model A, Tier II (adj.HR=3.65, P\u00a0=\u00a00.081), Tier III (adj.HR=6.65, P\u00a0=\u00a00.009), Tier IV (adj.HR=15.44, P\u00a0=\u00a00.001); and Model C, Tier II (adj.HR=3.47, P\u00a0=\u00a00.097), Tier III (adj.HR=6.50, P\u00a0=\u00a00.010), Tier IV (adj.HR=17.78, P\u00a0=\u00a00.002). In models lacking Ki-67, only SF-1(+) &amp;amp; T-PIT(+) (Model B, adj.HR=2.75, P\u00a0=\u00a00.037) and triple-TF positivity (Models B &amp;amp; D, adj.HR~3.80, P\u00a0=\u00a00.012) retained significance. Model E, Ki-67 \u22653% (adj.HR=1.76, P\u00a0=\u00a00.015) remained significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study validates critical prognostic synergy between TF multiplicity and elevated Ki-67 in PitNET recurrence. We propose a novel tiered molecular risk model anchored in this interaction. Whilst this synergy is best captured by the comprehensive Model A, the full spectrum of models (A\u2013E) provides a flexible diagnostic framework. This ensures risk stratification is accessible to pathology services with varying technical capabilities, to guide personalised post-operative management and surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1809624","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:24:48Z","timestamp":1785990288000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic prognostic value of transcription factor multiplicity and Ki-67 in pituitary neuroendocrine tumour recurrence after endoscopic transsphenoidal surgery: a novel tiered molecular risk model"],"prefix":"10.3389","volume":"17","author":[{"given":"Dan","family":"Taracha","sequence":"first","affiliation":[{"name":"Neurosurgery Department, General Hospital of Ningxia Medical University","place":["Yinchuan, China"]},{"name":"Ningxia Medical University","place":["Yinchuan, 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