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Both p16 and MTAP immunohistochemistry (IHC) are employed to assess <jats:italic>CDKN2A<\/jats:italic> loss, though each marker has limitations in accuracy to varying degrees.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study analyzed the concordance between molecular methods - DNA methylation profiling, molecular inversion probe (MIP) analysis, targeted next-generation sequencing (NGS), and fluorescence in situ hybridization (FISH) - and protein expression of p16 and MTAP in nine anaplastic meningiomas.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We showed that while p16 loss correlated well, MTAP protein was still expressed in three cases despite homozygous <jats:italic>CDKN2A<\/jats:italic> deletions. In those three cases the <jats:italic>MTAP<\/jats:italic> gene was hemizygously deleted. Additionally, a FISH probe encompassing both genes generated misleading results.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our results suggest that MTAP IHC can be unreliable as a sole surrogate for <jats:italic>CDKN2A<\/jats:italic> loss in anaplastic meningioma. Quantitative copy-number analysis via high-resolution chromosomal arrays enables precise determination of <jats:italic>CDKN2A<\/jats:italic> deletions. Given the therapeutic implications of WHO grading, accurate molecular testing is critical. We conclude that negative p16\/MTAP IHC in high-grade meningiomas should prompt molecular analysis for <jats:italic>CDKN2A<\/jats:italic> deletions, and MTAP IHC should not be solely relied upon for classification.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11060-025-05029-6","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T10:15:13Z","timestamp":1744625713000},"page":"769-776","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pitfalls in the evaluation of CDKN2A copy number status in meningioma"],"prefix":"10.1007","volume":"173","author":[{"given":"Valentina","family":"Zschernack","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea L.","family":"Friker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Goschzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"D\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Waha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vokuhl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Vatter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Pietsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"5029_CR1","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1038\/s41467-022-29397-z","volume":"13","author":"O Alhalabi","year":"2022","unstructured":"Alhalabi O, Chen J, Zhang Y, Lu Y, Wang Q, Ramachandran S, Tidwell RS, Han G, Yan X, Meng J, Wang R, Hoang AG, Wang W-L, Song J, Lopez L, Andreev-Drakhlin A, Siefker-Radtke A, Zhang X, Benedict WF, Shah AY, Wang J, Msaouel P, Zhang M, Guo CC, Czerniak B, Behrens C, Soto L, Papadimitrakopoulou V, Lewis J, Rinsurongkawong W, Rinsurongkawong V, Lee J, Roth J, Swisher S, Wistuba I, Heymach J, Wang J, Campbell MT, Efstathiou E, Titus M, Logothetis CJ, Ho TH, Zhang J, Wang L, Gao J (2022) MTAP deficiency creates an exploitable target for antifolate therapy in 9p21-loss cancers. 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