{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T20:28:37Z","timestamp":1784233717331,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T00:00:00Z","timestamp":1642291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland","award":["SN\/GW30\/2017"],"award-info":[{"award-number":["SN\/GW30\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To validate the reliability and implementation of an objective diagnostic method for giant cell tumour of bone (GCTB). H3-3A gene mutation testing was performed using two different methods, Sanger sequencing and immunohistochemical (IHC) assays. A total of 214 patients, including 120 with GCTB and 94 with other giant cell-rich bone lesions, participated in the study. Sanger sequencing and IHC with anti-histone H3.3 G34W and G34V antibodies were performed on formalin-fixed, paraffin-embedded tissues, which were previously decalcified in EDTA if needed. The sensitivity and specificity of the molecular method was 100% (95% CI: 96.97\u2013100%) and 100% (95% CI: 96.15\u2013100%), respectively. The sensitivity and specificity of IHC was 94.32% (95% CI: 87.24\u201398.13%) and 100% (95% CI: 93.94\u2013100.0%), respectively. P.G35 mutations were discovered in 2\/9 (22.2%) secondary malignant GCTBs and 9\/13 (69.2%) GCTB after denosumab treatment. We confirmed in a large series of patients that evaluation of H3-3A mutational status using direct sequencing is a reliable tool for diagnosing GCTB, and it should be incorporated into the diagnostic algorithm. Additionally, we discovered IHC can be used as a screening tool. Proper tissue processing and decalcification are necessary. The presence of the H3-3A mutation did not exclude malignant GCTB. Denosumab did not eradicate the neoplastic cell population of GCTB.<\/jats:p>","DOI":"10.3390\/ijms23020969","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:44:00Z","timestamp":1642365840000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Diagnostic Utility of Genetic and Immunohistochemical H3-3A Mutation Analysis in Giant Cell Tumour of Bone"],"prefix":"10.3390","volume":"23","author":[{"given":"Micha\u0142","family":"W\u0105grodzki","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Tysarowski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Seliga","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Wojnowska","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Stepaniuk","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Casta\u00f1eda Wysocka","sequence":"additional","affiliation":[{"name":"Department of Radiology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donata","family":"Maku\u0142a","sequence":"additional","affiliation":[{"name":"Department of Radiology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Pie\u0144kowski","sequence":"additional","affiliation":[{"name":"Department of Bone\/Soft Tissue Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart\u0142omiej","family":"Szostakowski","sequence":"additional","affiliation":[{"name":"Department of Bone\/Soft Tissue Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Zub","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8920-5429","authenticated-orcid":false,"given":"Piotr","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Department of Bone\/Soft Tissue Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,16]]},"reference":[{"key":"ref_1","unstructured":"Flanagan, A.M., Larousserie, F., O\u2019Donnell, P.G., and Yoshida, A. 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