{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:08:52Z","timestamp":1778476132670,"version":"3.51.4"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Recent studies have identified ATRX\/DAXX and PDX1\/ARX as biomarkers defining novel pancreatic neuroendocrine tumor (PanNET) subtypes, while the clinical significance of somatostatin receptors (SSTRs) remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 58 surgically resected primary PanNET samples and performed immunohistochemical evaluation of ATRX, DAXX, ARX\/PDX1, and SSTR2a\/5. The primary goal was to assess associations between biomarker expression and clinicopathological parameters. Secondary analyses explored relationships with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Quantitative expression scores were calculated, receiver operating characteristic (ROC) curve analysis was performed, and survival outcomes were assessed using Kaplan\u2013Meier analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The loss of DAXX or ATRX expression (86.3%) was more commonly observed in nonfunctional PanNETs cases compared to the functional PanNET group (13.7%) (p = 0.02). SSTR5 positive tumors were associated with longer median OS (73 vs. 7 months, p &amp;lt; 0.001) and RFS (36 vs. 6 months, p = 0.005). However, the difference in OS was not confirmed by Kaplan\u2013Meier analysis (log-rank p = 0.078). In PanNETs \u2265 2\u00a0cm, a tumor size cutoff of 2.45\u00a0cm predicted ATRX\/DAXX mutations with 96.9% sensitivity and 75% specificity (AUC 0.922, p = 0.007), in a cohort of 36 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ATRX\/DAXX loss was more prevalent in nonfunctional PanNETs (p = 0.02). Although SSTR5-positive tumors were associated with longer median OS, this difference was not confirmed by Kaplan\u2013Meier analysis. Furthermore, tumor size demonstrates predictive value for ATRX\/DAXX loss in PanNETs \u22652 cm, highlighting the relationship between tumor morphology and molecular alterations, however, this finding remains hypothesis-generating and requires further validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1820433","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:23:41Z","timestamp":1778473421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of ATRX, DAXX, PDX1, ARX, and somatostatin receptors in pancreatic neuroendocrine tumors: a clinicopathological study"],"prefix":"10.3389","volume":"17","author":[{"given":"Oana A.","family":"Ciobanu","sequence":"first","affiliation":[{"name":"Endocrinology Department, Carol Davila University of Medicine and Pharmacy","place":["Bucharest, Romania"]},{"name":"Endocrinology and Diabetes Mellitus, 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Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vlad","family":"Herlea","sequence":"additional","affiliation":[{"name":"Pathology Department, Fundeni Clinical Institute","place":["Bucharest, Romania"]},{"name":"Pathology Department, Carol Davila University of Medicine and Pharmacy","place":["Bucharest, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Tudose","sequence":"additional","affiliation":[{"name":"Pathology Department, Elias Hospital","place":["Bucharest, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florina","family":"Vasilescu","sequence":"additional","affiliation":[{"name":"Pathology Department, Central Military University Emergency Hospital","place":["Bucharest, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Sandra","sequence":"additional","affiliation":[{"name":"Oncology Department, Carol Davila University of Medicine and Pharmacy","place":["Bucharest, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen G.","family":"Barbu","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Carol Davila University of Medicine and Pharmacy","place":["Bucharest, Romania"]},{"name":"Endocrinology and Diabetes Mellitus, Nutrition and Metabolic Disorders Department, Elias Hospital","place":["Bucharest, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/S12022-022-09708-2","article-title":"Overview of the 2022 WHO classification of neuroendocrine neoplasms","volume":"33","author":"Rindi","year":"2022","journal-title":"Endocr Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.4377","article-title":"One hundred years after \u201ccarcinoid\u201d: Epidemiology of and prognostic factors for neuroendocrine 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