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Controversy remains over whether bone involvement negatively affects overall and progression\u2010free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin\u2010fixed paraffin\u2010embedded lymphoma lymph node samples from CHL patients were analyzed by nano\u2010liquid chromatography\u2013tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG\u2010avid lesions on a diagnostic FDG\u2010PET\/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth\/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin\u2010converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha\u2010X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.<\/jats:p>","DOI":"10.1111\/ejh.14326","type":"journal-article","created":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T02:54:14Z","timestamp":1728701654000},"page":"173-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomic Profiling of Lymph Nodes Differentiates Classic Hodgkin Lymphoma With and Without Skeletal Involvement"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0089-4273","authenticated-orcid":false,"given":"Maja Dam","family":"Andersen","sequence":"first","affiliation":[{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Wolter","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie Beck Hairing","family":"Enemark","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette Abildgaard","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"},{"name":"Department of Nuclear Medicine &amp; PET Centre Aarhus University Hospital  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Christian","family":"Gormsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine &amp; PET Centre Aarhus University Hospital  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina Lystlund","family":"Lauridsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f8rn","family":"Starklint","sequence":"additional","affiliation":[{"name":"Department of Medicine Regional Hospital Goedstrup  Herning Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen Jacques","family":"Hamilton\u2010Dutoit","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"},{"name":"Department of Pathology Aarhus University Hospital  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"d'Amore","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Ludvigsen","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bent","family":"Honor\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kamper","sequence":"additional","affiliation":[{"name":"Department of Haematology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.42.4036"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259\u2010014\u20102706\u2010x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy250"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097\u20100142(197610)38:4<1717::AID\u2010CNCR2820380445>3.0.CO;2\u20109"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.2.403"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2004.n.010"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.8800"},{"issue":"11","key":"e_1_2_10_9_1","first-page":"1860","article-title":"Report of the Committee on Hodgkin's Disease Staging Classification","volume":"31","author":"Carbone P. 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