{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:56:06Z","timestamp":1789152966964,"version":"build-2803163510"},"reference-count":66,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Ki-67 is a widely used marker of proliferation in meningiomas, influencing prognostic assessment and treatment decisions, including adjuvant radiation therapy. However, it is increasingly appreciated that some meningiomas are enriched with immune infiltration, which may confound Ki-67 interpretation as both immune and tumor cells exhibit proliferative potential. The authors aimed to dissect the cellular source and distribution of Ki-67 within the meningioma microenvironment and explore their clinical, genomic, and biological associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      The cellular composition of 32 resected meningiomas, including tumor and immune lineages, was profiled with single-cell mass cytometry (cytometry by time of flight [CyTOF]) and single-cell RNA sequencing (scRNAseq). The Ki-67 index and mitotic count were assessed by immunohistochemistry.\n                      <jats:italic>CDKN2A\/B<\/jats:italic>\n                      deletion and high-risk chromosome alterations were evaluated to establish a molecular Integrated Grade. An extrapolation cohort of 448 newly diagnosed meningiomas with gross-total resection was used for validation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Ki-67 is expressed by multiple cell lineages, both tumor and immune, as inferred by CyTOF on 77,498 cells and scRNAseq on 45,460 cells. The composition of cells contributing to Ki-67 expression changes from WHO grade 1 to grades 2 and 3, with Ki-67\n                      <jats:sup>+<\/jats:sup>\n                      cells in WHO grade 1 tumors composed of mostly myeloid-lineage cells, while nonimmune tumor cells dominated Ki-67\n                      <jats:sup>+<\/jats:sup>\n                      cells in grade 2 and 3 meningiomas. Ki-67 indices were markedly elevated in meningiomas from older patients (age &gt; 70 years) and influenced by the timing of radiation exposure. The optimal Ki-67 threshold associated with future recurrence varied with time of follow-up. Furthermore, the authors highlight two scenarios of focally elevated Ki-67 expression, central infarction and extramedullary hematopoiesis, in which apparent proliferation does not correlate with tumor aggressiveness.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>These findings unveil the complexity of Ki-67 expression in meningiomas, emphasizing the need for a nuanced interpretation of proliferation indices. The Ki-67 index remains a reliable parameter for assessing the clinical, molecular, and prognostic characteristics of meningiomas on careful evaluation and consideration of potential confounding factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2025.4.jns25438","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T01:29:52Z","timestamp":1753493392000},"page":"1325-1335","source":"Crossref","is-referenced-by-count":9,"title":["Ki-67 in meningioma: distribution and implications"],"prefix":"10.3171","volume":"143","author":[{"given":"Xiaopeng","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham, Harvard Medical School, Boston, Massachusetts;"},{"name":"Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruchit V.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Lederer","sequence":"additional","affiliation":[{"name":"Department of Surgery, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Meredith","sequence":"additional","affiliation":[{"name":"Department of Pathology, Mass General Brigham, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenya Linda","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mass General Brigham, Harvard Medical School, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"1","key":"b1","series-title":"Cancer Discov","first-page":"31","article-title":"Hallmarks of cancer: new dimensions","volume":"12","author":"Hanahan D","year":"2022","unstructured":"Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12(1):31\u201346."},{"issue":"5","key":"b2","series-title":"Cell","first-page":"646","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan D","year":"2011","unstructured":"Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674."},{"issue":"3","key":"b3","series-title":"J Cell Phys","first-page":"311","article-title":"The Ki-67 protein: from the known and the unknown","volume":"182","author":"Scholzen T","year":"2000","unstructured":"Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Phys. 2000;182(3):311\u2013322."},{"issue":"3","key":"b4","series-title":"Cell Prolif","first-page":"422","article-title":"Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis","volume":"40","author":"Rahmanzadeh R","year":"2007","unstructured":"Rahmanzadeh R, Huttmann G, Gerdes J, Scholzen T. Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis. Cell Prolif. 2007;40(3):422\u2013430."},{"issue":"7611","key":"b5","series-title":"Nature","first-page":"308","article-title":"Ki-67 acts as a biological surfactant to disperse mitotic chromosomes","volume":"535","author":"Cuylen S","year":"2016","unstructured":"Cuylen S, Blaukopf C, Politi AZ,  Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. Nature. 2016;535(7611):308\u2013312."},{"issue":"suppl 6","key":"b6","series-title":"Neuro Oncol","first-page":"vi1","article-title":"CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2017-2021","volume":"26","author":"Price M","year":"2024","unstructured":"Price M, Ballard C, Benedetti J,  CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2017-2021. Neuro Oncol. 2024;26(suppl 6):vi1-vi85."},{"issue":"8","key":"b7","series-title":"Neuro Oncol","first-page":"1231","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: a summary","volume":"23","author":"Louis DN","year":"2021","unstructured":"Louis DN, Perry A, Wesseling P,  The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231\u20131251."},{"key":"b8","series-title":"Neurosurgery","article-title":"Outcomes of radiosurgery for WHO grade 2 meningiomas: the role of Ki-67 index in guiding the tumor margin dose","author":"Meng Y","unstructured":"Meng Y, Bernstein K, Mashiach E,  Outcomes of radiosurgery for WHO grade 2 meningiomas: the role of Ki-67 index in guiding the tumor margin dose. Neurosurgery. 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