{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T18:37:23Z","timestamp":1786214243050,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Mirvetuximab soravtansine is an anti\u2010FOLR1 (folate receptor 1\/alpha) antibody\u2013drug conjugate with a companion diagnostic immunohistochemical (IHC) biomarker for platinum\u2010resistant ovarian, fallopian tube and primary peritoneal carcinoma. Its effectiveness has sparked interest in FOLR1 expression in endometrial carcinoma. We evaluate the relationship of FOLR1 and HER2\u2010IHC expression in high\u2010grade p53\u2010aberrantly expressed endometrial carcinomas, as overexpression of both is associated with high\u2010grade histologic features and aggressiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Carcinomas were scored for HER2\u2010IHC by both gastric and endometrial serous criteria and FOLR1\u2010IHC by Ventana package insert on tissue microarray cores. Intratumoral heterogeneity was quantified for HER2 and FOLR1 expression across multiple cores from the same tumour. A total of 291 cores (226 endometrial serous, 47 high\u2010grade endometrioid and 18 high\u2010grade M\u00fcllerian carcinoma, nos) were collected from 66 cases (discrete accession dates) from 62 patients. When stratified by two\u2010category HER2\u2010IHC status (0\/1+ vs. 2+\/3+, either criteria), significantly more HER2 2+\/3+ cores (16\/133, 12%) were FOLR1\u2010positive by a \u226575% cut\u2010off than HER2 0\/1+ specimens (8\/158, 5%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.031). Results were similar by a \u226525% cut\u2010off (49\/133, 37% vs. 38\/158, 24%;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.018). More cases with high HER2\u2010IHC heterogeneity (2\u20133\u2010pt difference) also demonstrated FOLR1\u2010IHC heterogeneity (\u226550% score difference between cores from the same case) than cases with no or low (1\u2010pt) HER2\u2010IHC heterogeneity, though most cases did not show high HER2 or FOLR1 intratumoral heterogeneity (16.7%\u201318.2% 2\u20133\u2010pt difference and 12.1% \u226550% score difference).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A positive correlation between HER2 and FOLR1 overexpression may be seen in high\u2010grade endometrial carcinomas with aberrant p53 expression, which may extend to intratumoral heterogeneity of biomarker expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/his.15533","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T02:39:05Z","timestamp":1754534345000},"page":"429-441","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Folate receptor alpha (\n                    <scp>FR\u03b1<\/scp>\n                    \/\n                    <scp>FOLR1<\/scp>\n                    ) and\n                    <scp>HER2<\/scp>\n                    immunohistochemical staining in high\u2010grade endometrial carcinoma with aberrant p53 expression"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-5192","authenticated-orcid":false,"given":"Austin","family":"McHenry","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8823-2804","authenticated-orcid":false,"given":"Brooke","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1554-2502","authenticated-orcid":false,"given":"Diane","family":"Libert","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4206-2002","authenticated-orcid":false,"given":"Phoebe M","family":"Hammer","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6488-9687","authenticated-orcid":false,"given":"Minami","family":"Tokuyama","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6610-1619","authenticated-orcid":false,"given":"Troy","family":"Tenney","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, College of Medicine The University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9764-8986","authenticated-orcid":false,"given":"Xiaoming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3537-8778","authenticated-orcid":false,"given":"Ann","family":"Folkins","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0935-7300","authenticated-orcid":false,"given":"Teri A.","family":"Longacre","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-6680","authenticated-orcid":false,"given":"Brooke E.","family":"Howitt","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-014-9539-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1254532"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/gyno.2002.6705"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2011.11.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047201"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970422)74:2<193::AID-IJC10>3.0.CO;2-F"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2007.05.018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.23686"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01900"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-23-0991"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2018-0459"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2017.08.015"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2017-0379"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2023.07.010"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2023.100299"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22113"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2020-0207-RA"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2016-0331-CP"},{"key":"e_1_2_9_20_1","unstructured":"TurashviliG KarnezisAN CrothersBet\u00a0al.Template for Reporting Results of Biomarker Testing of Specimens From Patients With Carcinoma of Gynecologic Origin Version 1.2.0.0 [Internet].2024College of American Pathologists (CAP) [cited 2025 May 10] Available from:https:\/\/documents.cap.org\/protocols\/Gynecologic.Bmk_1.2.0.0.\u2010REL.CAPCP.pdf?_gl=1*1o5n1mv*_ga*OTE0OTU3NzMyLjE3MjI0NzU5Mzg.*_ga_97ZFJSQQ0X*MTczNzU4NTAyMS4xNC4xLjE3Mzc1ODUwNTAuMC4wLjA."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61121-X"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000001115"},{"key":"e_1_2_9_23_1","unstructured":"VENTANA FOLR1 (FOLR1\u20102.1) RxDx Assay Interpretation Guide for Epithelial Ovarian Fallopian Tube or Primary Peritoneal Cancer 1015089US Rev A. 2022\u201011\u201014. 85755. 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Available from:https:\/\/usinfo.roche.com\/rs\/975\u2010FPO\u2010828\/images\/Interpretation%20guide%20FOLR1%20RxDx%20assay%2011.14.22%20BG%20FINAL.pdf?mkt_tok=OTc1LUZQTy04MjgAAAGMotMX0X81Vncw8JRZRt7j3mBo\u2010WZksHSLQOu4GuNFf3i0iNztpIHEIYBMtwAQ9wQzKEvlD25d5baVjGTOvrJO6fnxyxcSCbpRRBTVspxIDkXmDCo."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000000690"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2637-y"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/15330338221141795"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0000000000001053"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15164085"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002030"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15051435"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00746-5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2024-0277-LE"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.15533","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T08:15:45Z","timestamp":1765786545000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.15533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,6]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1111\/his.15533"],"URL":"https:\/\/doi.org\/10.1111\/his.15533","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,6]]},"assertion":[{"value":"2025-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}