{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:09:11Z","timestamp":1792714151392,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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                    <jats:italic>TP53<\/jats:italic>\n                    mutations are considered a surrogate biomarker of the serous\u2010like \u2018copy number high\u2019 molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations identified by next\u2010generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (\n                    <jats:italic>POLE<\/jats:italic>\n                    mut). A secondary aim assessed inter\u2010laboratory variability in p53 IHC. From a total of 207 cases from five centres (37\u201349 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009164) and curated tagged\u2010amplicon NGS\n                    <jats:italic>TP53<\/jats:italic>\n                    sequencing results (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009177). Following consensus review, local and central p53 IHC results were concordant in 156\/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild\u2010type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation was 155\/168 (92.3%) overall, and 117\/123 (95.1%) after excluding MMRd and\n                    <jats:italic>POLE<\/jats:italic>\n                    mut EC. Three (3\/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation. Subclonal mutant p53 IHC expression was observed in 9\/177 (5.1%) cases, of which four were either MMRd or\n                    <jats:italic>POLE<\/jats:italic>\n                    mut. Mutant pattern p53 IHC was observed in 63\/63 (100%) serous carcinomas that were MMR\u2010proficient\/\n                    <jats:italic>POLE<\/jats:italic>\n                    exonuclease domain wild\u2010type. Optimised p53 IHC performs well as a surrogate test for\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation in EC biopsies, demonstrates excellent inter\u2010laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC. \u00a9 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5375","type":"journal-article","created":{"date-parts":[[2019,12,12]],"date-time":"2019-12-12T07:17:38Z","timestamp":1576135058000},"page":"336-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":310,"title":["p53 immunohistochemistry is an accurate surrogate for\n                    <i>TP53<\/i>\n                    mutational analysis in endometrial carcinoma biopsies"],"prefix":"10.1002","volume":"250","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-1967","authenticated-orcid":false,"given":"Naveena","family":"Singh","sequence":"first","affiliation":[{"name":"Centre for Pathology Blizard Institute, Queen Mary University of London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M","family":"Piskorz","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Institute University of Cambridge  Cambridge UK"}],"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 University of Leiden  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mercedes","family":"Jimenez\u2010Linan","sequence":"additional","affiliation":[{"name":"Department of Pathology Addenbrooke's Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Rous","sequence":"additional","affiliation":[{"name":"Department of Pathology Addenbrooke's Hospital  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D","family":"Brenton","sequence":"additional","affiliation":[{"name":"Cancer Research UK Cambridge Institute University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Blake","family":"Gilks","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Vancouver General Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6615-2037","authenticated-orcid":false,"given":"Martin","family":"K\u00f6bel","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Calgary  Calgary Alberta 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