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We hypothesize that the acquisition of hybrid phenotypes displaying both epithelial and mesenchymal (E\/M) features may be involved in the malignant transformation and tumour dissemination in this subgroup. Therefore, we analysed, by digital pathology, the expression and prognostic significance of 3 classic cadherins (E-cadherin, epithelial marker; N-cadherin, mesenchymal marker; and P-cadherin, candidate marker of hybrid E\/M) in 577 formalin-fixed paraffin-embedded\u00a0human samples representing the putative stepwise serous carcinogenesis in the Fallopian tube epithelium (FTE). We observed a non-canonical N-to-P-cadherin switch along the carcinogenic progression, with a statistically significant overexpression of P-cadherin in pre-malignant and malignant samples, compared to the control FTE. Interestingly, this overexpression was most pronounced in precursor lesions and HGSC cells from malignant ascites. Tumours with high P-cadherin expression were significantly associated with worse overall survival, especially in the subgroup without\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    mutations. Transient P-cadherin knock-down resulted in in vitro significant reduction of functional hybrid E\/M hallmarks, namely decreased\n                    <jats:italic>anoikis<\/jats:italic>\n                    resistance, reduced collective migration and invasion in a representative platinum-resistant HRP cell line. Taken together, our results suggest that P-cadherin overexpression is an early event in the serous carcinogenesis and may be involved in hybrid E\/M activation in HRP-HGSC, further supporting this adhesion molecule as a promising biomarker for this poor prognostic subgroup.\n                  <\/jats:p>","DOI":"10.1007\/s00428-025-04104-7","type":"journal-article","created":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T20:39:53Z","timestamp":1746391193000},"page":"309-323","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["P-cadherin overexpression is associated with early transformation of the Fallopian tube epithelium and aggressiveness of tubo-ovarian high-grade serous carcinoma"],"prefix":"10.1007","volume":"488","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3563-7752","authenticated-orcid":false,"given":"Rita","family":"Can\u00e1rio","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9698-9233","authenticated-orcid":false,"given":"Ana Sofia","family":"Ribeiro","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0938-455X","authenticated-orcid":false,"given":"In\u00eas","family":"Morgado","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-5897","authenticated-orcid":false,"given":"Ana","family":"Peixoto","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2307-1018","authenticated-orcid":false,"given":"Ana","family":"Barbosa","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9102-757X","authenticated-orcid":false,"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-2277","authenticated-orcid":false,"given":"Nuno","family":"Mendes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-4143","authenticated-orcid":false,"given":"Paula","family":"Lopes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3482-2307","authenticated-orcid":false,"given":"Paula","family":"Monteiro","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9340-3612","authenticated-orcid":false,"given":"Ricardo","family":"Coelho","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0446-1942","authenticated-orcid":false,"given":"Francis","family":"Jacob","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4056-3225","authenticated-orcid":false,"given":"Viola","family":"Heinzelmann-Schwarz","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4091-2226","authenticated-orcid":false,"given":"Sara","family":"Ricardo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4896-5982","authenticated-orcid":false,"given":"Manuel R.","family":"Teixeira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0646-7667","authenticated-orcid":false,"given":"Carla","family":"Bartosch","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-1343","authenticated-orcid":false,"given":"Joana","family":"Paredes","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"4104_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41571-024-00881-3","volume":"21","author":"PM Webb","year":"2024","unstructured":"Webb PM, Jordan SJ (2024) Global epidemiology of epithelial ovarian cancer. 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