{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:43:18Z","timestamp":1790232198448,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/ http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:p>The 2021 World Health Organization classification of tumors of the central nervous system emphasizes the significance of molecular parameters for an integrated diagnosis. Homozygous deletion of cyclin-dependent kinase inhibitor 2a <jats:italic toggle=\"yes\">(CDKN2A)<\/jats:italic> has been associated with an adverse prognosis in <jats:italic toggle=\"yes\">IDH<\/jats:italic>-mutant gliomas, supratentorial ependymomas, meningiomas, and MPNST. In this study, we examined the value of p16 protein immunohistochemistry as a rapid and cost-effective screening tool for a homozygous <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic> deletion. Genetic analyses for <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic> in 30 pleomorphic xanthoastrocytomas, 32 <jats:italic toggle=\"yes\">IDH<\/jats:italic>-wild-type high-grade gliomas, 40 supratentorial ependymomas with <jats:italic toggle=\"yes\">ZFTA-RELA<\/jats:italic> gene fusion, 21 IDH-mutant astrocytomas, and 24 meningiomas were performed mainly by a molecular inversion probe assay, a high-resolution, quantitative technology for the assessment of chromosomal copy number alterations. Immunohistochemistry for p16 proved to have a high positive predictive value (range 90% to 100%) and an overall low negative predictive value (range 22% to 93%) for a homozygous <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic> deletion. In a setting where molecular testing is limited for cost and time reasons, p16 immunohistochemistry serves as a useful and rapid screening tool for identifying cases that should be subjected to further molecular testing for <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic> deletions.<\/jats:p>","DOI":"10.1097\/pas.0000000000002148","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T09:00:09Z","timestamp":1699606809000},"page":"46-53","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["p16 Immunohistochemistry as a Screening Tool for Homozygous CDKN2A Deletions in CNS Tumors"],"prefix":"10.1097","volume":"48","author":[{"given":"Valentina","family":"Zschernack","sequence":"first","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Andreiuolo","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"},{"name":"Instituto Estadual do C\u00e9rebro Paulo Niemeyer and the IDOR Institute, Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"D\u00f6rner","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wiedey","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"},{"name":"Department of Neurology, University of Bonn Medical Center, Bonn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie T.","family":"J\u00fcnger","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"},{"name":"Department of Neurosurgery, University of Cologne Medical Center, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea L.","family":"Friker","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Maruccia","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Pietsch","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, DGNN Brain Tumor Reference Center"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,11,10]]},"reference":[{"key":"R2-20250608","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cell.2006.10.003","article-title":"The regulation of INK4\/ARF in cancer and aging","volume":"127","author":"Kim","year":"2006","journal-title":"Cell"},{"key":"R3-20250608","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1073\/pnas.93.9.4350","article-title":"Inhibition of cyclin D-CDK4\/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity","volume":"93","author":"Khleif","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"R4-20250608","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1006\/excr.1997.3824","article-title":"The tumor suppressor protein p16INK4a","volume":"237","author":"Serrano","year":"1997","journal-title":"Exp Cell Res"},{"key":"R5-20250608","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.humpath.2015.12.021","article-title":"Practical issues in the application of p16 immunohistochemistry in diagnostic pathology","volume":"51","author":"Mahajan","year":"2016","journal-title":"Hum Pathol"},{"key":"R6-20250608","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1101\/gad.7.8.1572","article-title":"Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation","volume":"7","author":"Xiong","year":"1993","journal-title":"Genes & Development"},{"key":"R7-20250608","first-page":"545","article-title":"Mutations of cell cycle regulators. 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