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During recent decades, efforts have been made to improve the prognostic stratification of meningiomas by incorporating molecular data. A subgroup of tumors harboring a homozygous\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      deletion was identified, and a higher risk of tumor progression was observed, suggesting the potential use of cyclin-dependent kinases as biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>In this retrospective single-center study, the immunohistochemical staining for the cyclin-dependent kinases p16, phosphoRB1 (pRB1), CDK4 and CDK6 was analyzed in 1751 paraffin-embedded meningioma samples. For the assessment of p16, CDK4 and CDK6, a semi-quantitative score was applied, whereas an automated quantification tool was used for pRB1. The distribution and association with histopathological results, clinical data and progression-free survival (PFS)\u2014defined by radiographic tumor recurrence\u2014were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of all meningioma samples, 14.9% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009261) expressed p16. Elevated pRB1 levels were found in 34.5% (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009589) of tumor samples. CDK4 and CDK6 positive staining was observed in 41.9% and 42.2% of cases, respectively. Dichotomous stratification of meningiomas based on p16 and pRB1 expression levels suggested a significant influence on PFS in univariate analyses. Multivariate analysis determined elevated pRB1 expression, WHO grading, extent of resection, adjuvant radiotherapy, male gender, NF2-status and an elevated MIB1 index as independent prognostic factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High expression of pRB1 is an independent prognostic factor for shorter PFS. The prognostic impact of p16 is mostly attributed to the confounding increase of pRB1 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40478-026-02419-3","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:05:00Z","timestamp":1788419100000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The superior prognostic role of pRB1 over p16 immunohistochemistry as a biomarker in meningiomas"],"prefix":"10.1186","volume":"14","author":[{"given":"Hanna","family":"G\u00f6tt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Tellermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0306-1143","authenticated-orcid":false,"given":"Hannes","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4917-273X","authenticated-orcid":false,"given":"Peter","family":"Pa\u00dflack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elgin","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisa","family":"Di Francesco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2935-6919","authenticated-orcid":false,"given":"Daniel J.","family":"Merk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Honegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-8782","authenticated-orcid":false,"given":"Ghazaleh","family":"Tabatabai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Tatagiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-1276","authenticated-orcid":false,"given":"Felix","family":"Behling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-6209","authenticated-orcid":false,"given":"Jens","family":"Schittenhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"2419_CR1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106","author":"DN Louis","year":"2021","unstructured":"Louis DN et al (2021) The 2021 WHO classification of tumors of the central nervous system: a summary. 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