{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:57:43Z","timestamp":1776484663274,"version":"3.51.2"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T00:00:00Z","timestamp":1528934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["475969\/2013\u20108"],"award-info":[{"award-number":["475969\/2013\u20108"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","award":["E\u201026\/111.429\/2012"],"award-info":[{"award-number":["E\u201026\/111.429\/2012"]}],"id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hematological Oncology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The search for clinically relevant molecular markers in classical Hodgkin lymphoma (cHL) is hampered by the histopathological complexity of the disease, resulting from the admixture of a small number of neoplastic Hodgkin and Reed\u2010Sternberg (H\u2010RS) cells with an abundant and heterogeneous microenvironment. In this study, we evaluated gene expression profiles of 11 selected genes previously proposed as a molecular score for adult cHL, aiming to validate its application in the pediatric setting. Assays were performed by RT\u2010qPCR from formalin\u2010fixed paraffin\u2010embedded (FFPE) lymph nodes in 80 patients with cHL. Selected genes were associated with cell cycle (<jats:italic>CENPF<\/jats:italic>, <jats:italic>CDK1<\/jats:italic>, <jats:italic>CCNA2<\/jats:italic>, <jats:italic>CCNE2<\/jats:italic>, and <jats:italic>HMMR<\/jats:italic>), apoptosis (<jats:italic>BCL2<\/jats:italic>, <jats:italic>BCL2L1<\/jats:italic>, and <jats:italic>CASP3<\/jats:italic>), and monocytes\/macrophages (<jats:italic>LYZ<\/jats:italic> and <jats:italic>STAT1<\/jats:italic>). Despite using controlled preanalytical and analytical strategies, we were not able to validate the 11\u2010gene score to be applied in pediatric cHL. Principal component analysis (PCA) disclosed 3 components that accounted for 65.7% of the total variability. The second PC included microenvironment and apoptosis genes, from which <jats:italic>CASP3<\/jats:italic> expression was associated with a short time of progression\u2010free survival, which impact was maintained in the unfavorable risk group, Epstein\u2010Barr virus\u2010negative cases, and multivariate analysis (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). Because this is a counterintuitive association, CASP3 active expression was assessed at the protein level in H\u2010RS cells by double immunohistochemistry. In contrast to the association of mRNA levels with a poor therapeutic response, a high number of cleaved CASP3+ cells were associated with longer progression\u2010free survival (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.03) and overall survival (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.002). Our results demonstrate the feasibility of using FFPE samples as RNA source for molecular prognostication, but argue against the concept of direct and wide applicability of molecular scores in cHL. We reinforce the potential of CASP3 as an interesting target to be explored in adult and pediatric cHL, and alert for its dual biological role in H\u2010RS cells and tumor microenvironment.<\/jats:p>","DOI":"10.1002\/hon.2523","type":"journal-article","created":{"date-parts":[[2018,6,14]],"date-time":"2018-06-14T11:18:25Z","timestamp":1528975105000},"page":"663-670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pathway\u2010focused gene expression profiles and immunohistochemistry detection identify contrasting association of caspase 3 (CASP3) expression with prognosis in pediatric classical Hodgkin lymphoma"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-337X","authenticated-orcid":false,"given":"Gabriela","family":"Vera\u2010Lozada","sequence":"first","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center Instituto Nacional de C\u00e2ncer (INCA)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscilla","family":"Segges","sequence":"additional","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center Instituto Nacional de C\u00e2ncer (INCA)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio Gustavo","family":"Stefanoff","sequence":"additional","affiliation":[{"name":"Coordination of Clinical Research Instituto Nacional de C\u00e2ncer (INCA)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio Henrique M.","family":"Barros","sequence":"additional","affiliation":[{"name":"Institute for Pathology Unfallkrankenhaus Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerald","family":"Niedobitek","sequence":"additional","affiliation":[{"name":"Institute for Pathology Unfallkrankenhaus Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3782-3580","authenticated-orcid":false,"given":"Rocio","family":"Hassan","sequence":"additional","affiliation":[{"name":"Oncovirology Laboratory, Bone Marrow Transplantation Center Instituto Nacional de C\u00e2ncer (INCA)  Rio de Janeiro Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2542"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1586\/ehm.10.50"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(03)01320-2"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24851"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2011.08975.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-168096"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-1119"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-02-270009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.43.4589"},{"issue":"41","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","first-page":"67551","DOI":"10.18632\/oncotarget.11509","article-title":"Pediatric Hodgkin lymphoma\u2014biomarkers, drugs, and clinical trials for translational science and medicine","volume":"7","author":"Nagpal P","year":"2015","journal-title":"Oncotarget"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041588"},{"issue":"4","key":"e_1_2_8_13_1","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1042\/CS20050086","article-title":"Real\u2010time reverse transcription PCR (qRT\u2010PCR) and its potential use in clinical diagnosis","volume":"109","author":"Bustin SA","year":"2005","journal-title":"Clin Sci (Lond)"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.0352"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27314"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-07-641035"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2014.09.014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080908"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.1.36"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124531"},{"key":"e_1_2_8_23_1","volume-title":"Principles and practice of pediatric oncology","author":"Pizzo PA","year":"2015"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.16.9357"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13618"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2006.06.017"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2016.05.003"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2010.03705.x"},{"issue":"1","key":"e_1_2_8_29_1","first-page":"40","article-title":"Expression of the active caspase\u20103 in children and adolescents with classical Hodgkin lymphoma","volume":"50","author":"Cepelov\u00e1 M","year":"2014","journal-title":"Cesk Patol"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1869"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.055459"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.984"}],"container-title":["Hematological Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhon.2523","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hon.2523","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T14:00:05Z","timestamp":1694872805000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hon.2523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,14]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/hon.2523"],"URL":"https:\/\/doi.org\/10.1002\/hon.2523","archive":["Portico"],"relation":{},"ISSN":["0278-0232","1099-1069"],"issn-type":[{"value":"0278-0232","type":"print"},{"value":"1099-1069","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,14]]},"assertion":[{"value":"2017-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}