{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:57:35Z","timestamp":1792447055772,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,12]],"date-time":"2020-01-12T00:00:00Z","timestamp":1578787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"KWF Kankerbestrijding","doi-asserted-by":"publisher","award":["KWF\u2010YIG 8232\u201031648"],"award-info":[{"award-number":["KWF\u2010YIG 8232\u201031648"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Endometrial carcinoma (EC) molecular classification based on four molecular subclasses identified in The Cancer Genome Atlas (TCGA) has gained relevance in recent years due to its prognostic utility and potential to predict benefit from adjuvant treatment. While most ECs can be classified based on a single classifier (\n                    <jats:italic>POLE<\/jats:italic>\n                    exonuclease domain mutations\u00a0\u2013\u00a0\n                    <jats:italic>POLE<\/jats:italic>\n                    mut, MMR deficiency\u00a0\u2013\u00a0MMRd, p53 abnormal\u00a0\u2013\u00a0p53abn), a small but clinically relevant group of tumours harbour more than one molecular classifying feature and are referred to as \u2018multiple\u2010classifier\u2019 ECs. We aimed to describe the clinicopathological and molecular features of multiple\u2010classifier ECs with abnormal p53 (p53abn). Within a cohort of 3518 molecularly profiled ECs, 107 (3%) tumours displayed p53abn in addition to another classifier(s), including 64 with MMRd (MMRd\u2013p53abn), 31 with\n                    <jats:italic>POLE<\/jats:italic>\n                    mut (\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn), and 12 with all three aberrations (MMRd\u2013\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn). MMRd\u2013p53abn ECs and\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn ECs were mostly grade 3 endometrioid ECs, early stage, and frequently showed morphological features characteristic of MMRd or\n                    <jats:italic>POLE<\/jats:italic>\n                    mut ECs. 18\/28 (60%) MMRd\u2013p53abn ECs and 7\/15 (46.7%)\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn ECs showed subclonal p53 overexpression, suggesting that\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation was a secondary event acquired during tumour progression. Hierarchical clustering of TCGA ECs by single nucleotide variant (SNV) type and somatic copy number alterations (SCNAs) revealed that MMRd\u2013p53abn tumours mostly clustered with single\u2010classifier MMRd tumours (20\/23) rather than single\u2010classifier p53abn tumours (3\/23), while\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn tumours mostly clustered with single\u2010classifier\n                    <jats:italic>POLE<\/jats:italic>\n                    mut tumours (12\/13) and seldom with single\u2010classifier p53abn tumours (1\/13) (both\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.001, chi\u2010squared test). Finally, the clinical outcome of patients with MMRd\u2013p53abn and\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn ECs [stage I 5\u2010year recurrence\u2010free survival (RFS) of 92.2% and 94.1%, respectively] was significantly different from single\u2010classifier p53abn EC (stage I RFS 70.8%,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.024 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.050, respectively). Our results support the classification of MMRd\u2013p53abn EC as MMRd and\n                    <jats:italic>POLE<\/jats:italic>\n                    mut\u2013p53abn EC as\n                    <jats:italic>POLE<\/jats:italic>\n                    mut. \u00a9 2019 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5373","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T07:17:23Z","timestamp":1576135043000},"page":"312-322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":407,"title":["Clinicopathological and molecular characterisation of \u2018multiple\u2010classifier\u2019 endometrial carcinomas"],"prefix":"10.1002","volume":"250","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0873-5362","authenticated-orcid":false,"given":"Alicia","family":"Le\u00f3n\u2010Castillo","sequence":"first","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Gilvazquez","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics University of Oxford  Oxford UK"},{"name":"National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi","family":"Nout","sequence":"additional","affiliation":[{"name":"Department of Medical and Radiation Oncology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent THBM","family":"Smit","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N","family":"McAlpine","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Division of Gynecologic Oncology University of British Columbia and BC Cancer Agency  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"McConechy","sequence":"additional","affiliation":[{"name":"Contextual Genomics Inc  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kommoss","sequence":"additional","affiliation":[{"name":"Department of Women's Health T\u00fcbingen University Hospital  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Y","family":"Brucker","sequence":"additional","affiliation":[{"name":"Department of Women's Health T\u00fcbingen University Hospital  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2013Pathology, Karolinska Institutet, and Department of Pathology and Cytology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education Karolinska Institutet, and Department of Obstetrics and Gynaecology S\u00f6dersjukhuset  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilman T","family":"Rau","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A","family":"Soslow","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial Sloan Kettering Cancer Center  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6553-2855","authenticated-orcid":false,"given":"Raji","family":"Ganesan","sequence":"additional","affiliation":[{"name":"Department of Pathology Birmingham Women's NHS Foundation Trust  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Matias\u2010Guiu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital U Arnau de Vilanova and Hospital U de Bellvitge Universities of Lleida and Barcelona, IDIBELL, IRBLLEIDA, CIBERONC  Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Oliva","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital Harvard University  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth T","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4617-962X","authenticated-orcid":false,"given":"David N","family":"Church","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics University of Oxford  Oxford UK"},{"name":"National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Blake","family":"Gilks","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia and Vancouver General Hospital  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6881-8437","authenticated-orcid":false,"given":"Tjalling","family":"Bosse","sequence":"additional","affiliation":[{"name":"Department of Pathology Leiden University Medical Center  Leiden The 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