{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T10:12:07Z","timestamp":1788603127611,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007364","name":"Fondazione CRT","doi-asserted-by":"publisher","award":["113265\/2025.0323"],"award-info":[{"award-number":["113265\/2025.0323"]}],"id":[{"id":"10.13039\/100007364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Homozygous deletion (HD) of\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      represents an adverse prognostic biomarker in meningiomas and a diagnostic criterion for CNS WHO grade 3 assignment. However, fluorescence in\u00a0situ hybridisation (FISH) thresholds and the role of immunohistochemistry (IHC) surrogates remain uncertain. This study evaluated multiple\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      FISH cutoffs and assessed the diagnostic and prognostic performance of MTAP and p16 IHC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      Ninety\u2010two meningiomas (CNS WHO grades 1\u20133) were analysed by FISH evaluating \u2265\u200910%, \u2265\u200920% and \u2265\u200930%\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      HD thresholds.\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      HD was identified in 18.5%, 6.5% and 4.3% of cases using the respective cutoffs and was significantly associated with shorter disease\u2010specific survival across all thresholds (HD\u2009\u2265\u200910%\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001\n                      <jats:styled-content>;<\/jats:styled-content>\n                      HD\u2009\u2265\u200920%\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001; HD\u2009\u2265\u200930%\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.043). Patients with HD\u2009\u2265\u200920% and \u2265 30% experienced universal disease\u2010specific mortality within a median survival time of approximately 2 years. MTAP and p16 IHC were performed in matched areas. MTAP IHC showed high specificity (90%\u201392%) but limited sensitivity (30%\u201350%), while p16 IHC displayed variable sensitivity (41%\u201375%) and lower specificity (63%). Combined MTAP\/p16 negativity improved sensitivity (up to 100%) but reduced specificity (57%). Neither MTAP nor p16 loss correlated significantly with survival. Spatially heterogeneous IHC patterns corresponded to regional variability in\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      deletion by FISH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      HD detected by FISH, particularly using thresholds equal or greater than 20%, is strongly associated with poor outcome in meningiomas. MTAP and p16 IHC, alone or combined, lack sufficient accuracy as independent surrogates but may guide tissue selection for molecular testing in heterogeneous tumours.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.70101","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T09:25:07Z","timestamp":1788600307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Markers in Meningioma: Effectiveness of FISH\u2010Assessed\n                    <i>CDKN2A\/B<\/i>\n                    Homozygous Deletion and Limits of Surrogate p16\/MTAP Immunohistochemistry in Predicting Disease\u2010Specific Survival"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-0501","authenticated-orcid":false,"given":"Alessia Andrea","family":"Ricci","sequence":"first","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-1227","authenticated-orcid":false,"given":"Filippo","family":"Nozzoli","sequence":"additional","affiliation":[{"name":"Histopathology and Molecular Diagnostics Careggi University Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Biale","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Tampieri","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Verdun di Cantogno","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratory Medicine \u201cCitt\u00e0 della Salute e della Scienza\u201d University Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Garbossa","sequence":"additional","affiliation":[{"name":"Department of Neuroscience \u201cRita Levi Montalcini\u201d University of Turin  Turin Italy"},{"name":"Neurosurgery Unit \u201cCitt\u00e0 della Salute e della Scienza\u201d University Hospital, University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Levis","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9134-1537","authenticated-orcid":false,"given":"Roberta","family":"Rud\u00e0","sequence":"additional","affiliation":[{"name":"Division of Neuro\u2010Oncology, Department of Neuroscience \u201cRita Levi Montalcini\u201d University of Turin  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-7377","authenticated-orcid":false,"given":"Camilla","family":"Bonaudo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Careggi University Hospital  Florence Italy"},{"name":"Medical and Surgical Department, Department of Neurofarba University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Della Puppa","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Careggi University Hospital  Florence Italy"},{"name":"Medical and Surgical Department, Department of Neurofarba University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Livi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cM. 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