{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:06:17Z","timestamp":1789376777521,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06971"],"award-info":[{"award-number":["22K06971"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003769","name":"Eisai","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Histone methyltransferase EZH2 is essential for germinal center formation, and gain\u2010of\u2010function mutations of\n                    <jats:italic>EZH2<\/jats:italic>\n                    occur in approximately 20% of follicular lymphomas (FLs). Although EZH2 inhibitors are used for relapsed\/refractory\n                    <jats:italic>EZH2<\/jats:italic>\n                    \u2010mutated (\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>mut<\/jats:sup>\n                    ) FLs, their clinicopathological characteristics remain incompletely understood. We assessed the\n                    <jats:italic>EZH2<\/jats:italic>\n                    Y646 mutation by Sanger sequencing in 301 FLs and identified mutations in 17% (50\/301). Compared with\n                    <jats:italic>EZH2<\/jats:italic>\n                    wild\u2010type (\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>wt<\/jats:sup>\n                    ),\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>mut<\/jats:sup>\n                    FL showed a significantly higher proportion aged &gt;\u200960 years (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033). Pathologically,\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>mut<\/jats:sup>\n                    FL more frequently exhibited clear neoplastic follicles (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) and grater interfollicular tumor cell distributions highlighted by CD20 immunohistochemistry (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). These cases also more often showed the typical FL immunophenotype (CD10+, BCL2+, BCL6+) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.027) and BCL2 rearrangement (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0060). Gene expression profiling revealed enrichment of TNF\u2010\u03b1\/NF\u2010\u03baB signaling in\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>wt<\/jats:sup>\n                    FL, whereas\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>mut<\/jats:sup>\n                    FL showed upregulation of cell\u2010cycle programs, particularly the G2\/M checkpoint. Concordance of\n                    <jats:italic>EZH2<\/jats:italic>\n                    mutation status between primary and relapsed lesions was 94% (33\/35). Even at relapse,\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>mut<\/jats:sup>\n                    FL retained its characteristic pathological features, including clear follicles and high interfollicular spread of tumor cells. In conclusion,\n                    <jats:italic>EZH2<\/jats:italic>\n                    <jats:sup>mut<\/jats:sup>\n                    FL exhibits distinctive clinicopathological and molecular features that may help identify patients most likely to benefit from EZH2\u2010targeted therapy.\n                  <\/jats:p>","DOI":"10.1111\/pin.70167","type":"journal-article","created":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:29:39Z","timestamp":1787498979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Analysis of the Clinicopathological Features of Follicular Lymphoma With and Without\n                    <i>EZH2<\/i>\n                    Y646 Mutation"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-6087","authenticated-orcid":false,"given":"Akira","family":"Satou","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Nagoya University Hospital Nagoya Japan"},{"name":"Department of Surgical Pathology Aichi Medical University Hospital Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8748-6325","authenticated-orcid":false,"given":"Kanae","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Graduate School of Medicine Nagoya University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikki","family":"Mitsuda","sequence":"additional","affiliation":[{"name":"Department of Medicine University of the Ryukyus Okinawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akari","family":"Iwakoshi","sequence":"additional","affiliation":[{"name":"Department of Pathology National Hospital Organization Nagoya Medical Center Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Minoshima","sequence":"additional","affiliation":[{"name":"Department of Cytology and Molecular Pathology Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Gunji","sequence":"additional","affiliation":[{"name":"Department of Cytology and Molecular Pathology Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Cytology and Molecular Pathology Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6129-8299","authenticated-orcid":false,"given":"Joaquim","family":"Carreras","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Tokai University Isehara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Ikoma","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Tokai University Isehara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4332-5254","authenticated-orcid":false,"given":"Naoya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Tokai University Isehara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4855-4366","authenticated-orcid":false,"given":"Toyonori","family":"Tsuzuki","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Aichi Medical University Hospital Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Sato","sequence":"additional","affiliation":[{"name":"Oncology Department Medical Headquarters, Eisai Co. Ltd. Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-858X","authenticated-orcid":false,"given":"Kennosuke","family":"Karube","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Graduate School of Medicine Nagoya University Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21357"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1827.2000.01108.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12659"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.330"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1988.6.5.919"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1996.14.4.1333"},{"key":"e_1_2_11_8_1","first-page":"2876","article-title":"Frequent Detection of bcl\u20102\/JH Translocations in Human Blood and Organ Samples by a Quantitative Polymerase Chain Reaction Assay","volume":"55","author":"Ji W.","year":"1995","journal-title":"Cancer Research"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2001.19.2.420"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2856"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.518"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00169-2"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.311"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30441-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-496893"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028585"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1597"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09784"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70626"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.04.011"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.07.006"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2017.32"},{"key":"e_1_2_11_23_1","first-page":"3627","article-title":"Phase II Study of Tazemetostat for Relapsed or Refractory B\u2010Cell Non\u2010Hodgkin Lymphoma With EZH2 Mutation in Japan","volume":"112","author":"Izutsu K.","year":"2021","journal-title":"Cancer Prevention Research"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13223"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000332"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.23012"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-03-415380"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.23014"},{"key":"e_1_2_11_29_1","first-page":"E1116","article-title":"Mutations in Early Follicular Lymphoma Progenitors Are Associated With Suppressed Antigen Presentation","volume":"112","author":"Green M. R.","year":"2015","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-08-737361"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01029-x"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.04.004"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.032"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.05.022"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12983"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-015-1864-y"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002197"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-06-649905"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13674"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102278"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70167","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pin.70167","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70167","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:40:14Z","timestamp":1789375214000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.70167"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/pin.70167"],"URL":"https:\/\/doi.org\/10.1111\/pin.70167","archive":["Portico"],"relation":{},"ISSN":["1320-5463","1440-1827"],"issn-type":[{"value":"1320-5463","type":"print"},{"value":"1440-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70167"}}