PT  - JOURNAL ARTICLE
AU  - Alsaeed, Sami A
AU  - Toss, Michael
AU  - Alsaleem, Mansour
AU  - Aleskandarany, Mohammed
AU  - Joseph, Chitra
AU  - Kurozumi, Sasagu
AU  - Ball, Graham
AU  - Mongan, Nigel
AU  - Green, Andrew
AU  - Rakha, Emad
TI  - Prognostic significance of heat shock protein 90AA1 (HSP90α) in invasive breast cancer
AID  - 10.1136/jclinpath-2020-207106
DP  - 2022 Apr 01
TA  - Journal of Clinical Pathology
PG  - 263--269
VI  - 75
IP  - 4
4099  - http://jcp.bmj.com/content/75/4/263.short
4100  - http://jcp.bmj.com/content/75/4/263.full
SO  - J Clin Pathol2022 Apr 01; 75
AB  - 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 (HSP90α) encoded by the HSP90ΑA1 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 HSP90α 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 HSP90ΑA1 mRNA expression. HSP90α 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 HSP90ΑA1 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 HSP90α protein expression is an independent predictor of shorter BC-specific survival.Conclusion HSP90α can be used as a potential prognostic marker in BC. Further mechanistic studies are warranted to determine the underlying molecular mechanisms mediated by HSP90α in BC.All data relevant to the study are included in the article or uploaded as supplemental information. Research involving human participants and/or animals: the researchers of the current study did not perform any experiment on either human or animal subjects. The researchers validate that the information used in the current study is available on request.