{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:02:03Z","timestamp":1773270123893,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione CARISBO Project","award":["#19344"],"award-info":[{"award-number":["#19344"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The partial loss of SMARCB1\/INI1 expression has recently been reported in skull base conventional chordomas, with possible therapeutic implications. We retrospectively analyzed 89 patients with conventional spinal chordomas to investigate the differences in the immunohistochemical expression of SMARCB1\/INI1 and the underlying genetic alterations in the SMARCB1 gene. Moreover, we assessed the correlation of clinicopathological features (age, gender, tumor size, tumor location, surgical margins, Ki67 labelling index, SMARCB1\/INI1 pattern, previous surgery, previous treatment, type of surgery, and the Charlson Comorbidity Index) with patient survival. Our cohort included 51 males and 38 females, with a median age at diagnosis of 61 years. The median tumor size at presentation was 5.9 cm. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) rates were 90.8% and 54.9%, respectively. Partial SMARCB1\/INI1 loss was identified in 37 (41.6%) patients with conventional spinal chordomas (27 mosaic and 10 clonal). The most frequent genetic alteration detected was the monoallelic deletion of a portion of the long arm of chromosome 22, which includes the SMARCB1 gene. Partial loss of SMARCB1\/INI1 was correlated with cervical\u2013thoracic\u2013lumbar tumor location (p = 0.033) and inadequate surgical margins (p = 0.007), possibly due to the high degree of tumor invasiveness in this site. Among all the considered clinicopathological features related to patient survival, only tumor location in the sacrococcygeal region and adequate surgical margins positively impacted DFS. In conclusion, partial SMARCB1\/INI1 loss, mostly due to 22q deletion, was detected in a significant number of patients with conventional spinal chordomas and was correlated with mobile spine location and inadequate surgical margins.<\/jats:p>","DOI":"10.3390\/cancers16162808","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T08:54:08Z","timestamp":1723452848000},"page":"2808","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Conventional Spinal Chordomas: Investigation of SMARCB1\/INI1 Protein Expression, Genetic Alterations in SMARCB1 Gene, and Clinicopathological Features in 89 Patients"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-6019","authenticated-orcid":false,"given":"Margherita","family":"Maioli","sequence":"first","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-4621","authenticated-orcid":false,"given":"Stefania","family":"Cocchi","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8080-4484","authenticated-orcid":false,"given":"Marco","family":"Gambarotti","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Benini","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6430-1318","authenticated-orcid":false,"given":"Giovanna","family":"Magagnoli","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Gamberi","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8344-7534","authenticated-orcid":false,"given":"Cristiana","family":"Griffoni","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Ghermandi","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi Emanuele","family":"Noli","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Alcherigi","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7755-5085","authenticated-orcid":false,"given":"Cristina","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Experimental Oncology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6390-9762","authenticated-orcid":false,"given":"Giuseppe","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-2448","authenticated-orcid":false,"given":"Sofia","family":"Asioli","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum\u2014University of Bologna, 40126 Bologna, Italy"},{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elettra","family":"Pignotti","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1074-0155","authenticated-orcid":false,"given":"Alberto","family":"Righi","sequence":"additional","affiliation":[{"name":"Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"ref_1","unstructured":"WHO Classification of Tumours Editorial Board (2020). WHO Classification of Tumours 5th Edition: Soft Tissue and Bone Tumours, WHO Press. [5th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100771","DOI":"10.1016\/j.currproblcancer.2021.100771","article-title":"Chordoma: Current status, problems, and future directions","volume":"45","author":"Wedekind","year":"2021","journal-title":"Curr. Probl. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"386","DOI":"10.5858\/arpa.2020-0258-RA","article-title":"Chordoma","volume":"146","author":"Ulici","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/path.1969","article-title":"Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas","volume":"209","author":"Vujovic","year":"2006","journal-title":"J. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/gcc.22782","article-title":"Molecular characteristics of poorly differentiated chordoma","volume":"58","author":"Shih","year":"2019","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s00401-010-0767-x","article-title":"Loss of SMARCB1\/INI1 expression in poorly differentiated chordomas","volume":"120","author":"Mobley","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Righi, A., Cocchi, S., Maioli, M., Zoli, M., Guaraldi, F., Carretta, E., Magagnoli, G., Pasquini, E., Melotti, S., and Vornetti, G. (2023). SMARCB1\/INI1 loss in skull base conventional chordomas: A clinicopathological and molecular analysis. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1160764"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1136\/jclinpath-2016-203650","article-title":"Gene of the month: SMARCB1","volume":"69","author":"Kalimuthu","year":"2016","journal-title":"J. Clin. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.tig.2020.07.011","article-title":"Mammalian SWI\/SNF Chromatin Remodeling Complexes: Emerging Mechanisms and Therapeutic Strategies","volume":"36","author":"Centore","year":"2020","journal-title":"Trends Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1111\/cas.13173","article-title":"Oncogenic roles of SMARCB1\/INI1 and its deficient tumors","volume":"108","author":"Kohashi","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/1093526617749671","article-title":"SMARCB1-deficient Tumors of Childhood: A Practical Guide","volume":"21","author":"Pawel","year":"2018","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"662","DOI":"10.12688\/f1000research.24808.2","article-title":"SMARCB1\/INI1-deficient tumors of adulthood","volume":"9","author":"Parker","year":"2020","journal-title":"F1000Research"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1055\/s-0039-1693659","article-title":"Loss of SMARCB1 Expression Confers Poor Prognosis to Sinonasal Undifferentiated Carcinoma","volume":"81","author":"Chitguppi","year":"2020","journal-title":"J. Neurol. Surg. Part B Skull Base"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.humpath.2016.04.018","article-title":"Loss of INI1 expression in colorectal carcinoma is associated with high tumor grade, poor survival, BRAFV600E mutation, and mismatch repair deficiency","volume":"55","author":"Wang","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chen, S., Ulloa, R., Soffer, J., Alcazar-Felix, R.J., Snyderman, C.H., Gardner, P.A., Patel, V.A., and Polster, S.P. (2023). Chordoma: A Comprehensive Systematic Review of Clinical Trials. Cancers, 15.","DOI":"10.3390\/cancers15245800"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/gcc.22992","article-title":"Recurrent loss of chromosome 22 and SMARCB1 deletion in extra-axial chordoma: A clinicopathological and molecular analysis","volume":"60","author":"Wen","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Choy, E., MacConaill, L.E., Cote, G.M., Le, L.P., Shen, J.K., Nielsen, G.P., Iafrate, A.J., Garraway, L.A., Hornicek, F.J., and Duan, Z. (2014). Genotyping cancer-associated genes in chordoma identifies mutations in oncogenes and areas of chromosomal loss involving CDKN2A, PTEN, and SMARCB1. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101283"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1002\/gcc.22362","article-title":"Genomic aberrations frequently alter chromatin regulatory genes in chordoma","volume":"55","author":"Wang","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/gcc.22895","article-title":"Poorly differentiated chordoma with whole-genome doubling evolving from a SMARCB1- deficient conventional cordoma: A case report","volume":"60","author":"Curcio","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1097\/00003086-198011000-00013","article-title":"A system for the surgical staging of musculoskeletal sarcoma","volume":"153","author":"Enneking","year":"1980","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1097\/00007632-199705010-00020","article-title":"Primary bone tumors of the spine. Terminology and surgical staging","volume":"22","author":"Boriani","year":"1997","journal-title":"Spine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0021-9681(87)90171-8","article-title":"A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation","volume":"40","author":"Charlson","year":"1987","journal-title":"J. Chronic Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"153773","DOI":"10.1016\/j.prp.2022.153773","article-title":"CIC rearranged sarcomas: A single institution experience of the potential pitfalls in interpreting CIC FISH results","volume":"231","author":"Cocchi","year":"2022","journal-title":"Pathol. Res. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1002\/gcc.22376","article-title":"Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results","volume":"55","author":"Huang","year":"2016","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_25","first-page":"655","article-title":"Chordoma: The entity","volume":"1846","author":"Yakkioui","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1016\/S1470-2045(14)71190-8","article-title":"Building a global consensus approach to chordoma: A position paper from the medical and patient community","volume":"16","author":"Stacchiotti","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13045-020-00937-8","article-title":"EZH2: A novel target for cancer treatment","volume":"13","author":"Duan","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1093\/jnci\/djad141","article-title":"EZH2 inhibition: It\u2019s all about the context","volume":"115","author":"Rosen","year":"2023","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e12388","DOI":"10.1111\/cpr.12388","article-title":"Long non-coding RNA LOC554202 modulates chordoma cell proliferation and invasion by recruiting EZH2 and regulating miR-31 expression","volume":"50","author":"Ma","year":"2017","journal-title":"Cell Prolif."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Passeri, T., Dahmani, A., Masliah-Planchon, J., Naguez, A., Michou, M., El Botty, R., Vacher, S., Bouarich, R., Nicolas, A., and Polivka, M. (2022). Dramatic In Vivo Efficacy of the EZH2-Inhibitor Tazemetostat in PBRM1-Mutated Human Chordoma Xenograft. Cancers, 14.","DOI":"10.3390\/cancers14061486"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S1470-2045(18)30145-1","article-title":"Tazemetostat, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: A first-in-human, open-label, phase 1 study","volume":"19","author":"Italiano","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1158\/1078-0432.CCR-18-3133","article-title":"Immunologic Correlates of the Abscopal Effect in a SMARCB1\/INI1-negative Poorly Differentiated Chordoma after EZH2 Inhibition and Radiotherapy","volume":"25","author":"Gounder","year":"2019","journal-title":"Clin. Cancer Res."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/16\/2808\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:34:15Z","timestamp":1760110455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/16\/2808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,9]]},"references-count":32,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["cancers16162808"],"URL":"https:\/\/doi.org\/10.3390\/cancers16162808","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,9]]}}}