{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T18:22:44Z","timestamp":1783534964436,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"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>Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1\/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2\u2019s protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort (n = 1980) and TCGA cohort (n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p-values &lt; 0.0001), and shorter survival (p = 0.006), especially in luminal BC (p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival (p = 0.01). In DCIS, high nuclear\/low cytoplasmic co-expression showed significant association with a high tumour grade (p = 0.043), triple-negative and HER2-enriched molecular subtypes (p = 0.01), Comedo necrosis (p = 0.024), negative ER status (p = 0.004), negative PR status (p &lt; 0.0001), and a high proliferation index (p &lt; 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact.<\/jats:p>","DOI":"10.3390\/ijms25095053","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T15:05:01Z","timestamp":1715007901000},"page":"5053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers"],"prefix":"10.3390","volume":"25","author":[{"given":"Ayat","family":"Lashen","sequence":"first","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"},{"name":"Department of Pathology, Nottingham University Hospital, City Campus, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shatha","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Shoqafi","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashael","family":"Algethami","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie N.","family":"Jeyapalan","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"},{"name":"Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel P.","family":"Mongan","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"},{"name":"Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK"},{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-5525","authenticated-orcid":false,"given":"Emad A.","family":"Rakha","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"},{"name":"Department of Pathology, Nottingham University Hospital, City Campus, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5354-5480","authenticated-orcid":false,"given":"Srinivasan","family":"Madhusudan","sequence":"additional","affiliation":[{"name":"Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK"},{"name":"Department of Oncology, Nottingham University Hospitals, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1126\/science.2683079","article-title":"Checkpoints: Controls that ensure the order of cell cycle events","volume":"246","author":"Hartwell","year":"1989","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/35106065","article-title":"To cycle or not to cycle: A critical decision in cancer","volume":"1","author":"Malumbres","year":"2001","journal-title":"Nat. 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