{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:13:04Z","timestamp":1790521984683,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,10,5]],"date-time":"2017-10-05T00:00:00Z","timestamp":1507161600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008271","name":"LEO Pharma Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008271","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Every actinic keratosis (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>) starts with atypia at the basal layers of the epidermis (<jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> I). Progression into invasive squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">iSCC<\/jats:styled-content>) may occur following two main pathways, classical and differentiated. In the former, <jats:styled-content style=\"fixed-case\">iSCC<\/jats:styled-content> only occurs after involvement of the upper epidermal layers by atypical cells (<jats:styled-content style=\"fixed-case\">AK III<\/jats:styled-content>), while in the latter <jats:styled-content style=\"fixed-case\">iSCC<\/jats:styled-content> develops directly from <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> I. In the anogenital mucosa, these two pathways are associated with differential expression of p53 and p16.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To explore differences between both pathways in the pathogenesis of <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>, focusing on Ki67, p53, p16 and molecules that reveal epithelial\u2013mesenchymal transition (<jats:styled-content style=\"fixed-case\">EMT<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Tissue microarrays representative of superficial and deep portions of 80 consecutive <jats:styled-content style=\"fixed-case\">iSCC<\/jats:styled-content>s (53 <jats:styled-content style=\"fixed-case\">DP<\/jats:styled-content>\/27<jats:styled-content style=\"fixed-case\">CP<\/jats:styled-content>) were studied immunohistochemically using antibodies against Ki67, p53, p16, vimentin, E\u2010cadherin, \u03b2\u2010catenin and D2\u201040. The evaluation was performed by three researchers and the results compared to consensus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Invasive squamous cell carcinomas originated through the differentiated pathway exhibited significantly lower proliferative activity (Ki67) (30% vs 46%, <jats:italic>P<\/jats:italic> = 0.003) and significantly lower expression of vimentin (<jats:italic>P<\/jats:italic> &lt; 0.001), E\u2010cadherin (<jats:italic>P<\/jats:italic> &lt; 0.001) and membranous \u03b2\u2010catenin (<jats:italic>P<\/jats:italic> &lt; 0.001) than <jats:styled-content style=\"fixed-case\">iSCC<\/jats:styled-content>s developed through the classical pathway. The expression of E\u2010cadherin and membranous \u03b2\u2010catenin was significantly correlated (Pearson's <jats:italic>r<\/jats:italic> = 0.386, Spearman's Rho &lt; 0.001). There were no significant differences regarding the expressions of p53, p16 and D2\u201040.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Epithelial\u2013mesenchymal transition participates in transformation from <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> I into <jats:styled-content style=\"fixed-case\">iSCC<\/jats:styled-content> (differentiated pathway), whereas a higher proliferative capacity facilitates intraepidermal extension in the classical pathway. Podoplanin, which is also involved in tumour invasion, does not seem to play a differential role in either pathway. Finally, the absence of differences in p53 and p16 expressions is at variance with other epithelia where the classical pathway is associated with human papillomavirus infection and can be explained by the fact that both <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content> pathways share identical mechanisms of actinic oncogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.14514","type":"journal-article","created":{"date-parts":[[2017,8,10]],"date-time":"2017-08-10T16:42:40Z","timestamp":1502383360000},"page":"581-586","source":"Crossref","is-referenced-by-count":26,"title":["Epithelial\u2010to\u2010mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway, whereas proliferation plays a more significant role in the classical pathway"],"prefix":"10.1111","volume":"32","author":[{"given":"X.","family":"Saenz\u2010Sard\u00e0","sequence":"first","affiliation":[{"name":"Division of Oncology 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