{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:09:46Z","timestamp":1791295786962,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,1,23]],"date-time":"2017-01-23T00:00:00Z","timestamp":1485129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI14\/02043"],"award-info":[{"award-number":["PI14\/02043"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endometrial cancer is the most common gynaecological cancer in western countries, being the most common subtype of endometrioid tumours. Most patients are diagnosed at an early stage and present an excellent prognosis. However, a number of those continue to suffer recurrence, without means of identification by risk classification systems. Thus, finding a reliable marker to predict recurrence becomes an important unmet clinical issue. <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> is a cell\u2013cell adhesion molecule and member of the immunoglobulin superfamily that has been associated with the genesis of many cancers. Here, we first determined the value of <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> as a marker of recurrence in endometrioid endometrial cancer by conducting a retrospective multicentre study of 174 primary tumours. In early\u2010stage patients (<jats:italic>N<\/jats:italic> = 134), recurrence\u2010free survival was poorer in patients with <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content>\u2010positive compared to <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content>\u2010negative tumours (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 4.237; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.01\u201317.76). This difference was more significant in patients with early\u2010stage moderately\u2013poorly differentiated tumours (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 9.259; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 2.12\u201353.47). In multivariate analysis, <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> positivity was an independent prognostic factor in early\u2010stage disease (<jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content> 6.027; 95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.41\u201325.74). Then we demonstrated <jats:italic>in vitro<\/jats:italic> a role for <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> in cell migration and invasion by using a loss\u2010of\u2010function model in two endometrial cancer cell lines. <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> depletion resulted in a reduced primary tumour size and reduced metastatic local spread in an orthotopic murine model. Gene expression analysis of ALCAM\u2010depleted cell lines pointed to motility, invasiveness, cellular assembly, and organization as the most deregulated functions. Finally, we assessed some of the downstream effector genes that are involved in <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content>\u2010mediated cell migration; specifically <jats:italic><jats:styled-content style=\"fixed-case\">FLNB<\/jats:styled-content><\/jats:italic>, <jats:italic><jats:styled-content style=\"fixed-case\">TXNRD1<\/jats:styled-content><\/jats:italic>, and <jats:italic><jats:styled-content style=\"fixed-case\">LAMC2<\/jats:styled-content><\/jats:italic> were validated at the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein level. In conclusion, our results highlight the potential of <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> as a recurrent biomarker in early\u2010stage endometrioid endometrial cancer and point to <jats:styled-content style=\"fixed-case\">ALCAM<\/jats:styled-content> as an important molecule in endometrial cancer dissemination by regulating cell migration, invasion, and metastasis. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4851","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T01:23:01Z","timestamp":1479777781000},"page":"475-487","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Activated leukocyte cell adhesion molecule (<scp>ALCAM<\/scp>) is a marker of recurrence and promotes cell migration, invasion, and metastasis in early\u2010stage endometrioid endometrial cancer"],"prefix":"10.1002","volume":"241","author":[{"given":"Laura","family":"Devis","sequence":"first","affiliation":[{"name":"Biomedical Research Group in Gynecology, Vall Hebron Research Institute (VHIR) Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian P","family":"Moiola","sequence":"additional","affiliation":[{"name":"Biomedical Research Group in Gynecology, Vall Hebron Research 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