{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:19:54Z","timestamp":1773058794909,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Uterine clear cell carcinoma (CCC) consists of either pure clear cell histology but can also display other histological components (mixed uterine CCCs). In this study, the molecular and immunohistochemical background of pure and mixed uterine CCC was compared. Secondly, it was evaluated whether histological classification and molecular background affected clinical outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective multicenter study was performed comparing pure uterine CCCs (<jats:italic>n<\/jats:italic>\u2009=\u200922) and mixed uterine CCCs (<jats:italic>n<\/jats:italic>\u2009=\u200921). Targeted next\u2010generation sequencing using a 12\u2010gene targeted panel classified cases as polymerase\u2010\u03b5 (<jats:italic>POLE<\/jats:italic>) mutated, microsatellite instable (MSI), <jats:italic>TP53<\/jats:italic> wildtype or <jats:italic>TP53<\/jats:italic> mutated. Immunohistochemistry was performed for estrogen receptor, progesterone receptor, L1 cell adhesion molecule, MSH6, and PMS2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The following molecular subgroups were identified for pure and mixed uterine CCCs, respectively: <jats:italic>POLE<\/jats:italic> mutated 0% (0\/18) and 6% (1\/18); MSI in 6% (1\/18) and 50% (9\/18); <jats:italic>TP53<\/jats:italic> wildtype in 56% (10\/18) and 22% (4\/18); <jats:italic>TP53<\/jats:italic> mutated in 39% (7\/18) and 22% (4\/18) (<jats:italic>p<\/jats:italic>\u2009=\u20090.013). Patients with mixed CCCs had improved outcome compared to patients with pure CCCs. Frequent <jats:italic>TP53<\/jats:italic> mutations were found in pure CCCs and frequent MSI in mixed CCCs, associated with clinical outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Pure and mixed uterine CCCs are two entities with different clinical outcomes, which could be explained by different molecular backgrounds. These results underline the relevance of both morphological and molecular evaluation, and may assist in tailoring treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5937","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T05:19:42Z","timestamp":1682054382000},"page":"12365-12376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pure and mixed clear cell carcinoma of the endometrium: A molecular and immunohistochemical analysis study"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6873-7832","authenticated-orcid":false,"given":"Casper","family":"Reijnen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie W.","family":"Vrede","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Canisius\u2010Wilhelmina Hospital  Nijmegen The Netherlands"},{"name":"Department of Obstetrics and Gynaecology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Eijkelenboom","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruud","family":"Draak","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanne","family":"Sweegers","sequence":"additional","affiliation":[{"name":"Department of Pathology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc P. 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