{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:30:00Z","timestamp":1792798200469,"version":"4.5.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T00:00:00Z","timestamp":1491782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Promotionsprogramm \u201cExperimentelle Medizin\u201d der Universit\u00e4t Ulm","id":[{"id":"https:\/\/ror.org\/032000t02","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Giant cell tumour of the bone (\n                      <jats:styled-content style=\"fixed-case\">GCTB<\/jats:styled-content>\n                      ) is a neoplasm predominantly of long bones characterized by the H3F3A mutation G34W. Conventional diagnosis is challenged by the tumour's giant cell\u2010rich morphology, which overlaps with other giant cell\u2010containing lesions of the bone. Recently, a monoclonal antibody specific for the H3F3A mutation has been generated. Our aim was to test this antibody on a cohort of giant cell\u2010containing lesions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We used the antibody for analysis of 22 H3F3A\u2010mutated\n                      <jats:styled-content style=\"fixed-case\">GCTB<\/jats:styled-content>\n                      , including two patients with recurrences; for comparison we analysed a cohort of 36 H3F3A wild\u2010type giant cell\u2010rich lesions of the bone and soft tissue, containing one brown tumour, six aneurysmal bone cysts (\n                      <jats:styled-content style=\"fixed-case\">ABC<\/jats:styled-content>\n                      ), six chondroblastomas, five non\u2010ossifying\u2010fibromas, two fibrous dysplasias, nine tenosynovial giant cell tumours, one giant cell\u2010rich sarcoma and six osteosarcomas. Furthermore, among the 22 mutated cases, we included one\n                      <jats:styled-content style=\"fixed-case\">GCTB<\/jats:styled-content>\n                      with two recurrences and lung metastases; the patient was treated with the anti\u2010receptor activator of nuclear factor \u03baB (\n                      <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content>\n                      ) ligand denosumab. We show that all 22 H3F3A\u2010mutated\n                      <jats:styled-content style=\"fixed-case\">GCTB<\/jats:styled-content>\n                      display strong nuclear H3.3 G34W staining in the neoplastic component, while the osteoclastic giant cells are negative. 36 H3F3A wild\u2010type lesions are negative. The\n                      <jats:styled-content style=\"fixed-case\">GCTB<\/jats:styled-content>\n                      treated with denosumab revealed a reduction in the H3.3 G34W\u2010positive tumour cells and a decrease in osteoclastic giant cells accompanied by matrix and osteoid formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We conclude that positive H3.3 G34W staining is a specific and sensitive method for detection of H3F3A\u2010mutated\n                      <jats:styled-content style=\"fixed-case\">GCTB<\/jats:styled-content>\n                      . Denosumab treatment leads to a pathomorphosis of the lesion characterized by matrix and osteoid producing H3.3 G34W\u2010negative stromal cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.13190","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T01:49:13Z","timestamp":1487296153000},"page":"125-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["H3F3A mutation in giant cell tumour of the bone is detected by immunohistochemistry using a monoclonal antibody against the G34W mutated site of the histone H3.3 variant"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-6350","authenticated-orcid":false,"given":"Julian","family":"L\u00fcke","sequence":"first","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"von Baer","sequence":"additional","affiliation":[{"name":"Department of Surgery Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"L\u00fcbbeh\u00fcsen","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Breining","sequence":"additional","affiliation":[{"name":"Department of Radiology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Mellert","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Marienfeld","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schultheiss","sequence":"additional","affiliation":[{"name":"Department of Surgery Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"M\u00f6ller","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F E","family":"Barth","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ulm University Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,10]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Pathology and genetics of tumours of soft tissue and bone","author":"World Health Organization","year":"2017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-006-0215-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004320100234"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjp2.13"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-416721-6.00066-2"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000512"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7819-12-261"},{"key":"e_1_2_7_9_1","volume-title":"Dorfman and Czerniak's bone tumours","author":"Czerniak B","year":"2015"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-006-0204-x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.09.015"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2814"},{"key":"e_1_2_7_13_1","unstructured":"Dtsch Arztebl2003; 100: A 1632 [Heft 23]. 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