{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:05:29Z","timestamp":1789376729568,"version":"build-2803163510"},"reference-count":127,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"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"}],"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                    Morules were ordinally described as mulberry\u2010like clusters of endometrial metaplasia with the potential to differentiate toward true squamous metaplasia (SqM). Although both morular and SqM lesions are categorized under \u201cendometrial carcinoma (Em Ca) with squamous differentiation\u201d in the WHO classification, they represent biologically distinct entities. Notably, morules are strongly associated with\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    (\u03b2\u2010catenin) mutations. This review summarizes the molecular mechanisms driving the differentiation of Em Ca cells toward both morular and SqM phenotypes. Morules are frequently identified in younger Em Ca patients and display a unique immunophenotype characterized by nuclear \u03b2\u2010catenin accumulation, a lack of expression of estrogen\u2010\u03b1 and progesterone receptor expression, and a low proliferative index. In Em Ca cells harboring\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    alterations, the PTEN\/\u03b2\u2010catenin axis suppresses cell proliferation and induces epithelial\u2010to\u2010mesenchymal transition, promoting morule\u2010related cancer stem cell (CSC) properties. Conversely, p40 expression serves as the initial signaling event establishing SqM\u2010related CSC features within the morule\u2010SqM cascade. Furthermore, the ezrin\u2010radixin\u2010moesin\u2010binding phosphoprotein 50\/S100A4\/myosin heavy chain 9 axis drives terminal squamous differentiation, particularly under hypoxic conditions. Clinically, histopathological evaluation of morular morphology and nuclear \u03b2\u2010catenin status serves as a valuable tool for predicting progestin therapeutic efficacy in young Em Ca patients.\n                  <\/jats:p>","DOI":"10.1111\/pin.70168","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T18:17:33Z","timestamp":1787854653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Molecular Pathology of Morules in Endometrial Carcinoma: Biological Significance and Clinical Implications"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5366-7149","authenticated-orcid":false,"given":"Makoto","family":"Saegusa","sequence":"first","affiliation":[{"name":"Department of Pathology Kitasato University School of Medicine Sagamihara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"178","volume-title":"Handbuch der speziellen pathologischen anatomie und histologie","author":"Mayer R. H.","year":"1930"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/31.1.60"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.146"},{"key":"e_1_2_11_5_1","first-page":"EJ01","article-title":"Unveiling Morular Metaplasia of Endometrium: A Pathological Enigma","volume":"18","author":"Resmi P. R.","year":"2024","journal-title":"Journal of Clinical and Diagnostic Research"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13516"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2005.026237"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199708)182:4<429::AID-PATH872>3.0.CO;2-Z"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000171001.87599.e2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-0398"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-198403010-00007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000780"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2008.03083.x"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2010.085555"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.017996"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0b013e31826129e1"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153307"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007611-198205000-00022"},{"key":"e_1_2_11_19_1","first-page":"569","article-title":"Cytologic and Histologic Findings in Women Using an IUD","volume":"58","author":"Risse E. K.","year":"1981","journal-title":"Obstetrics and Gynecology"},{"key":"e_1_2_11_20_1","volume-title":"WHO Classification of Tumours of Female Genital Tumours","author":"The WHO Classification of Tumours Editorial Board","year":"2020"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001934"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880575"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000089421"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000004082"},{"key":"e_1_2_11_25_1","first-page":"19","article-title":"More Frequent Beta\u2010Catenin Exon 3 Mutations in Gallbladder Adenomas Than in Carcinomas Indicate Different Lineages","volume":"61","author":"Yanagisawa N.","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19911115)68:10<2293::AID-CNCR2820681032>3.0.CO;2-V"},{"key":"e_1_2_11_27_1","first-page":"549","article-title":"The Impact of Ki\u201067 Index, Squamous Differentiation, and Several Clinicopathologic Parameters on the Recurrence of Low and Intermediate\u2010Risk Endometrial Cancer","volume":"21","author":"Ocak B.","year":"2021","journal-title":"Bosnian Journal of Basic Medical Sciences\/Udru\u017eenje Basi\u010dnih Mediciniskih Znanosti = Association of Basic Medical Sciences"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2024.155804"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0220086"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-021-06382-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12113"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.5339\/qmj.2026.21"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2023.10.025"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.856"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63732-7"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2003.tb01360.x"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2026.03.008"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23695"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1581"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182256"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.21037\/cco-20-162"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12070990"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12081110"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205591"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2322"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36596-1"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.11.7340"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3220833"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.01.128"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405213200"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm105"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/375503a0"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0397-313"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22112"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(97)01305-X"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80031-3"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/26989"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1784"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1787"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1790"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700273"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00223-X"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.05.019"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn162"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02179-06"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2090-y"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.196"},{"key":"e_1_2_11_68_1","first-page":"263","article-title":"Cloning of Tetradecanoyl Phorbol Ester\u2010Induced 'Primary Response' Sequences and Their Expression in Density\u2010Arrested Swiss 3T3 Cells and a TPA Non\u2010Proliferative Variant","volume":"1","author":"Lim R. W.","year":"1987","journal-title":"Oncogene"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.13.4691"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.21.7857"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006827015320"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20257"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2404"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2570"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2009"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2023.11.014"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.909001"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00703-1"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri910"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200421358"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2198"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.2001.0287"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.9.2657"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0944rev"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.3.1230"},{"key":"e_1_2_11_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00507-4"},{"key":"e_1_2_11_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.18.5197"},{"key":"e_1_2_11_89_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e07-04-0391"},{"key":"e_1_2_11_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-023-00598-z"},{"key":"e_1_2_11_91_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300463200"},{"key":"e_1_2_11_92_1","first-page":"549","article-title":"CoCl2\u2010Induced HIF\u20101\u03b1 Expression Correlates With Proliferation and Apoptosis in MKN\u20101 Cells: A Possible Role for the PI3K\/Akt Pathway","volume":"29","author":"Ardyanto T.","year":"2006","journal-title":"International Journal of Oncology"},{"key":"e_1_2_11_93_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403057200"},{"key":"e_1_2_11_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2013.111"},{"key":"e_1_2_11_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2014.11.016"},{"key":"e_1_2_11_96_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-017-0211-0"},{"key":"e_1_2_11_97_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2001.280.3.F389"},{"key":"e_1_2_11_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2018.01.006"},{"key":"e_1_2_11_99_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00999-w"},{"key":"e_1_2_11_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114465"},{"key":"e_1_2_11_101_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5308.1943"},{"key":"e_1_2_11_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0497-356"},{"key":"e_1_2_11_103_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.247"},{"key":"e_1_2_11_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3330"},{"key":"e_1_2_11_105_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081018"},{"key":"e_1_2_11_106_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.12257"},{"key":"e_1_2_11_107_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc861"},{"key":"e_1_2_11_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601764"},{"key":"e_1_2_11_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80275-0"},{"key":"e_1_2_11_110_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3446"},{"key":"e_1_2_11_111_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaa1033"},{"key":"e_1_2_11_112_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0611376104"},{"key":"e_1_2_11_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2013.11.009"},{"key":"e_1_2_11_114_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-020-02944-z"},{"key":"e_1_2_11_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.08.063"},{"key":"e_1_2_11_116_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2786"},{"key":"e_1_2_11_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.116118"},{"key":"e_1_2_11_118_1","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13503"},{"key":"e_1_2_11_119_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0359-x"},{"key":"e_1_2_11_120_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081412"},{"key":"e_1_2_11_121_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0354379"},{"key":"e_1_2_11_122_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0500776"},{"key":"e_1_2_11_123_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19951115)76:10 <2044::AID-CNCR2820761323>3.0.CO;2-N"},{"key":"e_1_2_11_124_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19980701)83:1<111::AID-CNCR15>3.0.CO;2-#"},{"key":"e_1_2_11_125_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MP.0000092953.20717.48"},{"key":"e_1_2_11_126_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.05.072"},{"key":"e_1_2_11_127_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqae023"},{"key":"e_1_2_11_128_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-0436.1984.tb01402.x"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70168","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pin.70168","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:40:16Z","timestamp":1789375216000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.70168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":127,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/pin.70168"],"URL":"https:\/\/doi.org\/10.1111\/pin.70168","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":"2026-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70168"}}