{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T04:47:48Z","timestamp":1788410868464,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001111","name":"Cancer Australia","doi-asserted-by":"publisher","award":["1087165"],"award-info":[{"award-number":["1087165"]}],"id":[{"id":"10.13039\/501100001111","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endometrial carcinoma (EC) is the most common gynecological malignancy and fibroblast growth factor receptor 2 (FGFR2) is a frequently dysregulated receptor tyrosine kinase. FGFR2b and FGFR2c are the two main splice isoforms of FGFR2 and are normally localized in epithelial and mesenchymal cells, respectively. Previously, we demonstrated that <jats:italic>FGFR2c<\/jats:italic> mRNA expression was associated with aggressive tumor characteristics, shorter progression\u2010free survival (PFS), and disease\u2010specific survival (DSS) in endometrioid ECs (EECs). The objectives of this study were to investigate the spatial expression of FGFR2b in normal and hyperplasia with and without atypia of human endometrium and to assess the prognostic significance of FGFR2b expression in EC. <jats:italic>FGFR2b<\/jats:italic> and <jats:italic>FGFR2c<\/jats:italic> mRNA expression was evaluated in normal (proliferative [<jats:italic>n<\/jats:italic>\u00a0=\u00a010], secretory [<jats:italic>n<\/jats:italic>\u00a0=\u00a015], and atrophic [<jats:italic>n<\/jats:italic>\u00a0=\u00a010] endometrium), hyperplasia with and without atypia (<jats:italic>n<\/jats:italic>\u00a0=\u00a019) as well as two patient cohorts of EC samples (discovery [<jats:italic>n<\/jats:italic>\u00a0=\u00a078] and Vancouver [<jats:italic>n<\/jats:italic>\u00a0=\u00a0460]) using isoform\u2010specific BaseScope RNA <jats:italic>in situ<\/jats:italic> hybridization assays. Tumors were categorized based on <jats:italic>FGFR2<\/jats:italic> isoform expression (one, both, or neither) and categories were correlated with clinicopathologic markers, molecular subtypes, and clinical outcomes. The <jats:italic>FGFR2b<\/jats:italic> splice isoform was exclusively expressed in the epithelial compartment of normal endometrium and hyperplasia without atypia. We observed <jats:italic>FGFR2c<\/jats:italic> expression at the basalis layer of glands in 33% (3\/9) of hyperplasia with atypia. In patients with EEC, FGFR2b+\/FGFR2c\u2212 expression was found in 48% of the discovery cohort and 35% of the validation Vancouver cohort. In univariate analyses, tumors with FGFR2b+\/FGFR2c\u2212 expression had longer PFS (hazard ratio [HR] 0.265; 95% CI 0.145\u20130.423; log\u2010rank <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.019) and DSS (HR 0.31; 95% CI 0.149\u20130.622; log\u2010rank <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) compared to tumors with FGFR2b\u2212\/FGFR2c+ expression in the large EEC Vancouver cohort. In multivariable Cox regression analyses, tumors with FGFR2b+\/FGFR2c\u2212 expression were significantly associated with longer DSS (HR 0.37; 95% CI 0.153\u20130.872; log\u2010rank <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.023) compared to FGFR2b\u2212\/FGFR2c+ tumors. In conclusion, FGFR2b+\/FGFR2c\u2212 expression is associated with favorable clinicopathologic markers and clinical outcomes suggesting that FGFR2b could play a role in tailoring the management of EEC patients in the clinic if these findings are confirmed in an independent cohort.<\/jats:p>","DOI":"10.1002\/cjp2.286","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T04:46:39Z","timestamp":1658465199000},"page":"521-537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Spatial expression of the <scp><i>FGFR2b<\/i><\/scp> splice isoform and its prognostic significance in endometrioid endometrial carcinoma"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-2171","authenticated-orcid":false,"given":"Asmerom T","family":"Sengal","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Faculty of Health Queensland University of Technology (QUT) located at the Translational Research Institute (TRI)  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Smith","sequence":"additional","affiliation":[{"name":"Mater Pathology Mater Research and University of Queensland  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron E","family":"Snell","sequence":"additional","affiliation":[{"name":"Mater Pathology Mater Research and University of Queensland  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Talhouk","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Division of 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