Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer

Lashen, Ayat G; Toss, Michael S; Wootton, Louisa; Green, Andrew R.; Mongan, Nigel P; Madhusudan, Srinivasan; Rakha, Emad

Abstract

Background: Polo-like kinase-1 (PLK1) plays a crucial role in cell cycle progression,and it is considered a potential therapeutic target in many cancers. Although the role of PLK1 is well established in triple negative breast cancer (TNBC) as an oncogene, its role in luminal BC is still controversial. In this study, we aimed to evaluate the prognostic and predictive role of PLK1 in BC and its molecular subtypes.

Methods: A large BC cohort (n=1208) were immunohistochemically stained for PLK1. The association with clinicopathological, molecular subtypes and survival data was analysed. PLK1 mRNA was evaluated in the publicly available datasets (n=6774), including The Cancer Genome Atlas and the Kaplan–Meier Plotter tool.

Results: 20% of the study cohort showed high cytoplasmic PLK1 expression. High PLK1 expression was significantly associated with better outcome in the whole cohort, luminal BC. In contrast, high PLK1 expression was associated with poor outcome in TNBC. Multivariate analyses indicated that high PLK1 expression is independently associated with longer survival in luminal BC, and in poorer prognosis in TNBC. At the mRNA levels, PLK1 expression was associated with short survival in TNBC consistent with the protein expression. However, in luminal BC, its prognostic value significantly
varies between cohorts.

Conclusion: The prognostic role of PLK1 in BC is molecular subtype dependent. As PLK1 inhibitors are introduced to clinical trials for several cancer types, our study supports evaluation of pharmacological inhibition of PLK1 as an attractive therapeutic
target in TNBC. However, in luminal BC, PLK1 prognostic role remains controversial.

Citation

Lashen, A. G., Toss, M. S., Wootton, L., Green, A. R., Mongan, N. P., Madhusudan, S., & Rakha, E. (2023). Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer. Histopathology, 83(3), 414-425. https://doi.org/10.1111/his.14960

• Journal Article Type: Article
• Acceptance Date: May 9, 2023
• Online Publication Date: May 24, 2023
• Publication Date: 2023-09
• Deposit Date: May 16, 2023
• Publicly Available Date: May 25, 2024
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 83
• Issue: 3
• Pages: 414-425
• DOI: https://doi.org/10.1111/his.14960
• Public URL: https://nottingham-repository.worktribe.com/output/20832146
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/his.14960