{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T02:43:23Z","timestamp":1780713803254,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cellular senescence is a stress-induced cell-cycle arrest that constrains expansion of ultraviolet-damaged keratinocytes yet can remodel the microenvironment. This systematic review evaluated histological and genetic or epigenetic senescence markers in actinic keratosis (AK), cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). PubMed, Scopus, and Web of Science were searched (January 2005\u2013May 2025); 34 human studies were included. AK showed an early senescent signature with frequent cyclin-dependent kinase inhibitor p21 (p21CIP1) expression (82.1%) and DNA damage signaling, including phosphorylated histone H2AX (gamma-H2AX) positivity (77%). In invasive cSCC, p21CIP1 fell to 43.9% and tumor suppressor p53 immunoreactivity often declined, whereas cyclin-dependent kinase inhibitor p16 (p16INK4a) commonly accumulated without arrest, including cytoplasmic staining at invasion fronts. Reported escape pathways involved c-Jun N-terminal kinase 2 activity and long noncoding RNA PVT1\u2013dependent repression of p21. Telomerase reverse transcriptase (TERT) promoter mutations were prevalent in cSCC (about 50%) and BCC (up to 78%) but uncommon in AK, consistent with late telomerase activation. Study heterogeneity, variable antibody scoring, and limited assessment of senescence-associated beta-galactosidase and secretory mediators restricted cross-study comparability. Standardized, spatially resolved profiling may refine risk stratification and support senescence-targeted prevention and therapy in keratinocyte cancers.<\/jats:p>","DOI":"10.3390\/ijms27031520","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:02:01Z","timestamp":1770195721000},"page":"1520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Histological and Genetic Markers of Cellular Senescence in Keratinocyte Cancers and Actinic Keratosis: A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3775-8021","authenticated-orcid":false,"given":"Piotr","family":"Sobolewski","sequence":"first","affiliation":[{"name":"Dermatology Clinic, National Medical Institute of the Ministry of Interior and Administration, 02-507 Warsaw, Poland"},{"name":"Chair and Clinic of Dermatology and Pediatric Dermatology, Centre of Postgraduate Medical Education, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Koper","sequence":"additional","affiliation":[{"name":"Chair and Clinic of Dermatology and Pediatric Dermatology, Centre of Postgraduate Medical Education, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wasaznik-Jedras","sequence":"additional","affiliation":[{"name":"Pathomorphological Center, National Institute of Medicine of the Ministry of Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Kolos","sequence":"additional","affiliation":[{"name":"Pathomorphological Center, National Institute of Medicine of the Ministry of Interior and Administration, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Walecka","sequence":"additional","affiliation":[{"name":"Dermatology Clinic, National Medical Institute of the Ministry of Interior and Administration, 02-507 Warsaw, Poland"},{"name":"Chair and Clinic of Dermatology and Pediatric Dermatology, Centre of Postgraduate Medical Education, 02-507 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.jid.2022.11.017","article-title":"Senescence induced by UVB in keratinocytes impairs amino acids balance","volume":"143","author":"Bauwens","year":"2023","journal-title":"J. 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