{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:01:39Z","timestamp":1781798499997,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2016.041.3"],"award-info":[{"award-number":["2016.041.3"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2016.041.2"],"award-info":[{"award-number":["2016.041.2"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2016.041.1"],"award-info":[{"award-number":["2016.041.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Testicular germ cell tumours are the most common solid malignancies in young men of age 14\u201344\u2009years. It is generally accepted that both seminomas and non\u2010seminomas arise from a common precursor, the germ cell neoplasia <jats:italic>in\u2010situ<\/jats:italic>, which itself is the result of a defective (primordial) germ cell development. The stem cell\u2010like population of the non\u2010seminomas, the embryonal carcinoma, is capable of the differentiation of all three germ layers (teratomas) and extra\u2010embryonic tissues (yolk\u2010sac tumours, choriocarcioma) into cells. In contrast, seminomas are thought to have a limited differentiation potential. Nevertheless, several studies have highlighted their ability to undergo reprogramming to an embryonal carcinoma or differentiation into other non\u2010seminomatous entities. Here, we demonstrate that in approximately 5% of seminomas, the yolk\u2010sac tumour driver gene FOXA2 is detectable at the protein level, indicative of an occult yolk\u2010sac tumour subpopulation that putatively arose from seminoma cells, as the presence of other GCT entities could be excluded. The presence of these subpopulations might render the tumour more aggressive and argue for an adjustment of the therapeutic concept. We used our data to update the model of germ cell tumour pathogenesis, especially regarding the developmental potential of seminomas. Additionally, we suggest to include detection of FOXA2 into standard routine diagnosis of seminomas.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14933","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T14:47:46Z","timestamp":1685717266000},"page":"477-481","source":"Crossref","is-referenced-by-count":18,"title":["Updating germ cell tumour pathogenesis\u2009\u2013\u2009the ability of seminomas for FOXA2\u2010driven extra\u2010embryonic differentiation"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0367-6527","authenticated-orcid":false,"given":"Felix","family":"Bremmer","sequence":"first","affiliation":[{"name":"Institute of Pathology, University Medical Center Goettingen  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Lubk","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Goettingen  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-8060","authenticated-orcid":false,"given":"Philipp","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center Goettingen  Goettingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-845X","authenticated-orcid":false,"given":"Daniel","family":"Nettersheim","sequence":"additional","affiliation":[{"name":"Department of Urology, Urological Research Laboratory, Translational UroOncology Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0029-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajur.2020.05.009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.21958"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2011.01172.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1005415"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.05.013"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9903"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11050728"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16222"},{"key":"e_1_2_7_11_1","article-title":"TCGA","author":"The Cancer Genomee\u00a0Atlas","year":"2013","journal-title":"Natl Cancer Inst Natl Hum Genome Res Inst"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14258"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-3952(22)04459-3"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14560"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17575-w"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/11769351221132634"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14933","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T05:27:59Z","timestamp":1691645279000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14933"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,2]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/his.14933"],"URL":"https:\/\/doi.org\/10.1111\/his.14933","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,2]]}}}