{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T04:06:46Z","timestamp":1763611606706,"version":"3.45.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Several studies analyzed the \u201creprogramming\u201d of germ cell tumors of the testis (GCTT), known to be an epigenetic process that results in the preservation of stem cell features and\/or differentiation of GCTT. EZH2 is a methyltransferase involved in the epigenetic regulation of tumors and has become a promising therapeutic target, but few studies have analyzed its expression in GCTT, germ cell neoplasia in situ (GCNIS), and adjacent testis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested 131, 36, and 29 GCTT components, GCNIS, and adjacent testes, respectively. EZH2 expression was evaluated by H-score and compared between different subgroups by adopting median values and the Fisher exact test.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that EZH2 was more highly expressed by adjacent testis\/GCNIS rather than by GCTT (P\u2005&amp;lt;\u2005.001), with adjacent testis showing the highest values and being statistically significant compared to GCNIS (P\u2005&amp;lt;\u2005.001). In adjacent testis, EZH2 expression was mainly detected in spermatocytes (primary and secondary) and spermatids, with scattered positive spermatogonia. Seminoma\/embryonal carcinoma showed statistically significantly higher EZH2 expression compared to the other nonseminomatous GCTT (P\u2005=\u2005.027).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EZH2 is differentially expressed during GCTT reprogramming (adjacent testis [very high levels] \u2192 GCNIS [high levels] \u2192 seminoma\/embryonal carcinoma [moderate levels] \u2192 other nonseminomatous GCTT [low\/absent levels]), supporting its involvement in the epigenetic regulation for determining the fate of GCTT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqaf098","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T11:53:46Z","timestamp":1755777226000},"page":"739-745","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemical expression of EZH2 in germ cell tumors of the testis: New insights into the genesis and epigenetic reprogramming of these fascinating tumors"],"prefix":"10.1093","volume":"164","author":[{"given":"Sofia","family":"Melotti","sequence":"first","affiliation":[{"name":"Pathology Unit, DIAP-Dipartimento Interaziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna , Bologna ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9046-1115","authenticated-orcid":false,"given":"Francesca","family":"Ambrosi","sequence":"additional","affiliation":[{"name":"Pathology Unit, DIAP-Dipartimento Interaziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna , Bologna ,","place":["Italy"]},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna , Bologna 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Epigenetics Group, Research Center of IPO Porto (GEBC CI-IPOP)\/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)\/Porto Comprehensive Cancer Center (P.CCC) , Porto ,","place":["Portugal"]},{"name":"Department of Pathology and Molecular Immunology, ICBAS-School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP) , Porto ,","place":["Portugal"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-150X","authenticated-orcid":false,"given":"Michelangelo","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Pathology Unit, DIAP-Dipartimento Interaziendale di Anatomia Patologica di Bologna, Maggiore Hospital-AUSL Bologna , Bologna ,","place":["Italy"]},{"name":"Department of Medical and Surgical Sciences (DIMEC), University of Bologna , Bologna 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