Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?

https://m2.mtmt.hu/ eng 2026-10-23 16:05 JournalArticle 32051117 VALIDATED true 11st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary Department of Biomedical Informatics, Center for Preventive Medicine and Digital Health, Mannheim, Germany Department of Neuroradiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany Department of Orthopedics, Semmelweis University, Budapest, Hungary Department of Anatomic Pathology and Experimental Pathology, University Ziekenhuis, Brussels, Belgium Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy Cited By :3 Export Date: 3 February 2023 CODEN: POREF Correspondence Address: Krenacs, T.; 11st Department of Pathology and Experimental Cancer Research, Hungary; email: krenacst@gmail.com 0 false 2026-10-21T10:22:21.693+0000 2022-07-22T10:17:34.673+0000 2021-06-02T09:34:25.155+0000 true 10062250 Molnár-Taga Márta /api/admin/10062250 Admin Márta Molnár-Taga (SE 4-es admin) true 10062250 2026-08-19T06:57:09.450+0000 2022-07-22T10:17:34.897+0000 true 10062250 Molnár-Taga Márta /api/admin/10062250 Admin Márta Molnár-Taga (SE 4-es admin) true 10062250 true false true 24 24 /api/publicationtype/24 PublicationType Journal Article 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Journal Article 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Article (Journal Article) 101 true 10000059 true 1 /api/category/1 Category Scientific true 1 Maros, Mate E. Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate? true true /api/journal/1035680 REVIEWED PATHOLOGY AND ONCOLOGY RESEARCH 1219-4956 1532-2807 true false 1035680 false 1035680 true 1219-4956 1532-2807 Journal FOREIGN_AND_HUNGARIAN 27 643146 643146 11 2021 Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15(INK4b), p16(INK4a), p27(KIP1), p53 through its effector p21(WAF1) and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB. Funding 2010131 /api/funding/2010131 (LSHC-CT- 2006-018814) false true true true 2021 true true true false true false GOLD 2026-10-21 true https://doi.org/10.3389/pore.2021.643146 7 0 7 5 0 7 6 7 7 7 7 5 5 5 2 0 7 5 7 5 0 7 7 Folyóiratcikk Journal Article 24 7 Könyvrészlet Chapter in Book 25 0 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2021 0 2 1 2 1 2022 0 0 0 0 0 2023 0 2 2 2 2 2024 0 1 1 1 1 2025 0 2 1 2 1 Q2 false 10004796,10004659 false false false 2021-06-01T09:47:26.667+0000 I. Sz. Patológiai és Kísérleti Rákkutató Intézet (SE / AOK / I); Ortopédiai Klinika (SE / AOK / K) 6 19 2 10 0 true Language 10002 /api/language/10002 English Angol English true 2 true PersonAuthorship 96497370 /api/authorship/96497370 Maros, Mate E. [Maros, Máté Előd (Patológia), author] I. Department of Pathology and experimental Can... (SU / FM / I) 1 0.1 true false false Author 10080571 /api/author/10080571 Máté Előd Maros (Patológia) Maros Máté Előd true true Maros Mate E. true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497371 /api/authorship/96497371 Balla, Peter [Balla, Péter (Tumorbiológia), author] I. Department of Pathology and experimental Can... (SU / FM / I) 2 0.1 false false false Author 10032338 /api/author/10032338 Péter Balla (Tumorbiológia) Balla Péter true 10032338 true Balla Peter true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497372 /api/authorship/96497372 Micsik, Tamas [Micsik, Tamás (Patológia), author] I. Department of Pathology and experimental Can... (SU / FM / I) 3 0.1 false false false Author 10025105 /api/author/10025105 Tamás Micsik (Patológia) Micsik Tamás true 10025105 true Micsik Tamas true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497373 /api/authorship/96497373 Sapi, Zoltan [Sápi, Zoltán (Patológia), author] I. Department of Pathology and experimental Can... (SU / FM / I) 4 0.1 false false false Author 10004659 /api/author/10004659 Zoltán Sápi (Patológia) Sápi Zoltán true 10004659 true Sapi Zoltan true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497374 /api/authorship/96497374 Szendroi, Miklos [Szendrői, Miklós (Ortopédia: felnőt...), author] Department of Orthopedics (SU / FM / C) 5 0.1 false false false Author 10004796 /api/author/10004796 Miklós Szendrői (Ortopédia: felnőtt ortopédia, csont- és lágyrész daganatok, csípő- és térd-artroplasztika) Szendrői Miklós true 10004796 true Szendroi Miklos true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497375 /api/authorship/96497375 Wenz, Holger 6 0.1 false false false Wenz Holger true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497376 /api/authorship/96497376 Groden, Christoph 7 0.1 false false false Groden Christoph true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497377 /api/authorship/96497377 Forsyth, Ramses G. 8 0.1 false false false Forsyth Ramses G. true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497378 /api/authorship/96497378 Picci, Piero 9 0.1 false false false Picci Piero true false false AuthorshipType 1 /api/authorshiptype/1 Author 0 true 0 true false true PersonAuthorship 96497379 /api/authorship/96497379 Krenacs, Tibor ✉ [Krenács, Tibor (Sejtbiológia, imm...), author] I. Department of Pathology and experimental Can... 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(2021) PATHOLOGY AND ONCOLOGY RESEARCH 1219-4956 1532-2807 27<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" mtid="10080571"><a href="/gui2/?type=authors&mode=browse&sel=10080571" target="_blank">Maros Mate E. (<span class="authorship-author-name">Maros Máté Előd</span> <span class="authorAux-mtmt"> Patológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/I. Department of Pathology and experimental Cancer Research</span> ;    <span class="author-name" mtid="10032338"><a href="/gui2/?type=authors&mode=browse&sel=10032338" target="_blank">Balla Peter (<span class="authorship-author-name">Balla Péter</span> <span class="authorAux-mtmt"> Tumorbiológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/I. Department of Pathology and experimental Cancer Research</span> ;    <span class="author-name" mtid="10025105"><a href="/gui2/?type=authors&mode=browse&sel=10025105" target="_blank">Micsik Tamas (<span class="authorship-author-name">Micsik Tamás</span> <span class="authorAux-mtmt"> Patológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/I. Department of Pathology and experimental Cancer Research</span> ;    <span class="author-name" mtid="10004659"><a href="/gui2/?type=authors&mode=browse&sel=10004659" target="_blank">Sapi Zoltan (<span class="authorship-author-name">Sápi Zoltán</span> <span class="authorAux-mtmt"> Patológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/I. Department of Pathology and experimental Cancer Research</span> ;    <span class="author-name" mtid="10004796"><a href="/gui2/?type=authors&mode=browse&sel=10004796" target="_blank">Szendroi Miklos (<span class="authorship-author-name">Szendrői Miklós</span> <span class="authorAux-mtmt"> Ortopédia: felnőtt ortopédia, csont- és lágyrés...</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Clinical">C</span>/Department of Orthopedics</span> ;    <span class="author-name" >Wenz Holger </span> ;    <span class="author-name" >Groden Christoph </span> ;    <span class="author-name" >Forsyth Ramses G. </span> ;    <span class="author-name" >Picci Piero </span> ;    <span class="author-name" mtid="10007878"><a href="/gui2/?type=authors&mode=browse&sel=10007878" target="_blank">Krenacs Tibor ✉ (<span class="authorship-author-name">Krenács Tibor</span> <span class="authorAux-mtmt"> Sejtbiológia, immunológia, pathológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis University">SU</span>/<span title="Faculty of Medicine">FM</span>/<span title="Instituties">I</span>/I. Department of Pathology and experimental Cancer Research</span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32051117" target="_blank">Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?</a></div> <div> <span class="journal-title">PATHOLOGY AND ONCOLOGY RESEARCH</span> <span class="journal-issn">(<a target="_blank" href="https://portal.issn.org/resource/ISSN/1219-4956">1219-4956</a> <a target="_blank" href="https://portal.issn.org/resource/ISSN/1532-2807">1532-2807</a>)</span>: <span class="journal-volume">27</span> <span class="page"> Paper 643146. 11 p. </span> <span class="year">(2021)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Language: English | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.3389/pore.2021.643146" target="_blank" href="https://doi.org/10.3389/pore.2021.643146"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000650985100001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000650985100001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85105985896" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85105985896"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="34257609" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=34257609&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Journal subject: Scopus - Medicine (miscellaneous)   Rank: Q2</div> <div class="journal-subject">Journal subject: Scopus - Pathology and Forensic Medicine   Rank: Q2</div> <div class="journal-subject">Journal subject: Scopus - Cancer Research   Rank: Q3</div> <div class="journal-subject">Journal subject: Scopus - Oncology   Rank: Q3</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="" class="citingPub-count">Citing papers: 7</span> | Independent citation: 5 | Self citation: 2 | Unknown citation: 0 | Number of citations in WoS: 7 | Number of citations in Scopus: 7 | WoS/Scopus assigned: 7 | Number of citations with DOI: 6 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32051117&sort=publishedYear,desc&sort=title"> Number of cited publications: 7 </a> </div> <div class="mtid"><span class="long-pub-mtid">Publication: 32051117</span> | <span class="status-data status-VALIDATED"> Validated </span> Core Citing | <span class="type-subtype">Journal Article ( Article ) </span> | <span class="pub-category">Scientific</span> | <span class="publication-sourceOfData">WOS TAGGED</span> </div> <div class="funder"> (LSHC-CT- 2006-018814) </div> <div class="lastModified">Last Modified: 2022.07.22. 12:17 Márta Molnár-Taga (SE 4-es admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Comments</u>: 11st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary Department of Biomedical Informatics, Center for Preventive Medicine and Digital Health, Mannheim, Germany Department of Neuroradiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany Department of ...</pre> </div></div>