Prognostic significance of heat shock protein 90AA1 (HSP90?) in invasive breast cancer

Alsaeed, Sami A.; Toss, Michael; Alsaleem, Mansour; Aleskandarany, Mohammed; Joseph, Chitra; Kurozumi, Sasagu; Ball, Graham; Mongan, Nigel; Green, Andrew; Rakha, Emad

Abstract

Aims: The mechanisms that drive breast cancer (BC) progression and poor outcome are not fully understood. The human heat shock protein 90 alpha family class A member 1 (HSP90?) encoded by the HSP90 'A1 gene has a vital role in cellular responses to stress and is implicated in the development and progression of many cancers. The current study aims to explore the clinical and prognostic importance of HSP90? in BC. Methods: The Molecular Taxonomy of Breast Cancer International Consortium (n=1980); The Cancer Genome Atlas (n=1097) and the Breast Cancer Gene-Expression Miner (Bc-GenExMiner) BC datasets (n=5056) were used to evaluate HSP90 'A1 mRNA expression. HSP90? protein expression was further assessed using immunohistochemistry in a large (n=911) well-characterised BC series. The association between mRNA and protein expressions with other clinicopathological parameters and outcome was analysed. Results: High expression of HSP90 'A1 both at the mRNA and protein levels was significantly associated with characteristics of BC poor prognosis, including high grade, lymphovascular invasion, poor Nottingham Prognostic Index and positive expression of p53 and PIK3CA. Outcome analysis revealed that high HSP90? protein expression is an independent predictor of shorter BC-specific survival. Conclusion: HSP90? can be used as a potential prognostic marker in BC. Further mechanistic studies are warranted to determine the underlying molecular mechanisms mediated by HSP90? in BC.

Citation

Alsaeed, S. A., Toss, M., Alsaleem, M., Aleskandarany, M., Joseph, C., Kurozumi, S., …Rakha, E. (2022). Prognostic significance of heat shock protein 90AA1 (HSP90α) in invasive breast cancer. Journal of Clinical Pathology, 75(4), 263-269. https://doi.org/10.1136/jclinpath-2020-207106

• Journal Article Type: Article
• Acceptance Date: Jan 23, 2021
• Online Publication Date: Mar 25, 2021
• Publication Date: 2022-04
• Deposit Date: May 14, 2021
• Publicly Available Date: Mar 25, 2021
• Journal: Journal of Clinical Pathology
• Print ISSN: 0021-9746
• Electronic ISSN: 1472-4146
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 75
• Issue: 4
• Pages: 263-269
• DOI: https://doi.org/10.1136/jclinpath-2020-207106
• Keywords: General Medicine; Pathology and Forensic Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/5530683
• Publisher URL: https://jcp.bmj.com/content/75/4/263