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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

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’s 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 < 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 < 0.0001), and a high proliferation index (p < 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.

Details

Title
Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers
Author
Lashen, Ayat 1 ; Alqahtani, Shatha 2 ; Shoqafi, Ahmed 2 ; Algethami, Mashael 2 ; Jeyapalan, Jennie N 3 ; Mongan, Nigel P 4 ; Rakha, Emad A 1   VIAFID ORCID Logo  ; Srinivasan Madhusudan 5   VIAFID ORCID Logo 

 Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; [email protected] (A.L.); [email protected] (S.A.); [email protected] (A.S.); [email protected] (M.A.); [email protected] (J.N.J.); [email protected] (N.P.M.); [email protected] (E.A.R.); Department of Pathology, Nottingham University Hospital, City Campus, Nottingham NG5 1PB, UK 
 Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; [email protected] (A.L.); [email protected] (S.A.); [email protected] (A.S.); [email protected] (M.A.); [email protected] (J.N.J.); [email protected] (N.P.M.); [email protected] (E.A.R.) 
 Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; [email protected] (A.L.); [email protected] (S.A.); [email protected] (A.S.); [email protected] (M.A.); [email protected] (J.N.J.); [email protected] (N.P.M.); [email protected] (E.A.R.); Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK 
 Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; [email protected] (A.L.); [email protected] (S.A.); [email protected] (A.S.); [email protected] (M.A.); [email protected] (J.N.J.); [email protected] (N.P.M.); [email protected] (E.A.R.); Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington LE12 5RD, UK; Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA 
 Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, University Park, Nottingham NG7 3RD, UK; [email protected] (A.L.); [email protected] (S.A.); [email protected] (A.S.); [email protected] (M.A.); [email protected] (J.N.J.); [email protected] (N.P.M.); [email protected] (E.A.R.); Department of Oncology, Nottingham University Hospitals, Nottingham NG5 1PB, UK 
First page
5053
Publication year
2024
Publication date
2024
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3053185875
Copyright
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.