{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:11:53Z","timestamp":1775715113078,"version":"3.50.1"},"reference-count":28,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Bernese foundation of clinical-experimental tumor research","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2024,9,7]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Mutations affecting exon 3 of the \u03b2-catenin (\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      ) gene result in constitutive activation of WNT signalling and are a diagnostic hallmark of several tumour entities including desmoid-type fibromatosis. They also define clinically relevant tumour subtypes within certain entities, such as endometrioid carcinoma. In diagnostics, \u03b2-catenin immunohistochemistry is widely used as a surrogate for\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      mutations. Yet, it is often difficult to assess in practice, given that the characteristic nuclear translocation may be focal or hard to distinguish from the spillover of the normal membranous staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We therefore examined lymphoid enhancer-binding factor 1 (LEF1) immunostaining, a nuclear marker of WNT activation that serves as a potential surrogate for\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In a cohort of endometrial carcinomas with known mutation status (n=130) LEF1 was 85% accurate in predicting\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      mutation status (64% sensitivity, 90% specificity) while \u03b2-catenin was 76% accurate (72% sensitivity; 77% specificity). Across a variety of entities characterised by\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      mutations as putative drivers, we found diffuse and strong expression of LEF1 in 77% of cases. LEF1 immunostaining proved easier to interpret than \u03b2-catenin immunostaining in 54% of cases, more difficult in 1% of cases and comparable in the remaining cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      We conclude that LEF1 immunostaining is a useful surrogate marker for\n                      <jats:italic>CTNNB1<\/jats:italic>\n                      mutations. It favourably complements \u03b2-catenin immunohistochemistry and outperforms the latter as a single marker.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jcp-2024-209695","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T13:25:21Z","timestamp":1733750721000},"page":"12-18","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Lymphoid enhancer-binding factor 1 (LEF1) immunostaining as a surrogate for \u03b2-catenin (\n                    <i>CTNNB1<\/i>\n                    ) mutations"],"prefix":"10.1136","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9128-0364","authenticated-orcid":false,"given":"Ekkehard","family":"Hewer","sequence":"first","affiliation":[{"name":"Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"},{"name":"Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascal David","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7982-8713","authenticated-orcid":false,"given":"Erik","family":"Vassella","sequence":"additional","affiliation":[{"name":"Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Knabben","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Bern University Hospital and University of Bern, Bern, Switzerland, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Imboden","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Bern University Hospital and University of Bern, Bern, Switzerland, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D","family":"Mueller","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Bern University Hospital and University of Bern, Bern, Switzerland, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-950X","authenticated-orcid":false,"given":"Tilman T","family":"Rau","sequence":"additional","affiliation":[{"name":"Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland"},{"name":"Institute of Pathology, Heinrich Heine University and University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-1392","authenticated-orcid":false,"given":"Matthias S","family":"Dettmer","sequence":"additional","affiliation":[{"name":"Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland"},{"name":"Institute of Pathology, Klinikum Stuttgart, Stuttgart, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,12,9]]},"reference":[{"key":"2025121502100671000_79.1.12.1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-014-0954-y"},{"key":"2025121502100671000_79.1.12.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03932.x"},{"key":"2025121502100671000_79.1.12.3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2007.02794.x"},{"key":"2025121502100671000_79.1.12.4","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.15"},{"key":"2025121502100671000_79.1.12.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0080-0"},{"key":"2025121502100671000_79.1.12.6","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqy178"},{"key":"2025121502100671000_79.1.12.7","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2018.6956"},{"key":"2025121502100671000_79.1.12.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.10.030"},{"key":"2025121502100671000_79.1.12.9","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2015-202862"},{"key":"2025121502100671000_79.1.12.10","doi-asserted-by":"publisher","DOI":"10.1111\/his.12150"},{"key":"2025121502100671000_79.1.12.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0626-9"},{"key":"2025121502100671000_79.1.12.12","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlaa004"},{"key":"2025121502100671000_79.1.12.13","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"2025121502100671000_79.1.12.14","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2004088.Integrative"},{"key":"2025121502100671000_79.1.12.15","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-017-0873-3"},{"key":"2025121502100671000_79.1.12.16","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-023-09775-z"},{"key":"2025121502100671000_79.1.12.17","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001513"},{"key":"2025121502100671000_79.1.12.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2019.11.013"},{"key":"2025121502100671000_79.1.12.19","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1790"},{"key":"2025121502100671000_79.1.12.20","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3880374"},{"key":"2025121502100671000_79.1.12.21","doi-asserted-by":"publisher","DOI":"10.1111\/cup.13806"},{"key":"2025121502100671000_79.1.12.22","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13096"},{"key":"2025121502100671000_79.1.12.23","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-024-03782-z"},{"key":"2025121502100671000_79.1.12.24","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12030555","article-title":"The 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