The prognostic significance of lysosomal protective protein (Cathepsin A) in breast ductal carcinoma in situ

Toss, Michael S.; Miligy, Islam M.; Haj-Ahmad, Rita; Gorringe, Kylie L.; AlKawaz, Abdulbaqi; Mittal, Karuna; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad A.

Abstract

Background: Cathepsin A (CTSA) is a key regulatory enzyme for galactoside metabolism. Additionally, it has a distinct proteolytic activity and plays a role in tumour progression. CTSA is differentially expressed at the mRNA level between breast ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). In this study, we aimed to characterise CTSA protein expression in DCIS and evaluate its prognostic significance.
Methods: A large cohort of DCIS (n=776 for pure DCIS and n=239 for DCIS associated with IBC (DCIS/IBC)) prepared as tissue microarray was immunohistochemically stained for CTSA.
Results: High CTSA expression was observed in 48% of pure DCIS. High expression was associated with features of poor DCIS prognosis including younger age at diagnosis (less than 50 years), higher nuclear grade, hormone receptor negativity, HER2 positivity, high proliferative index and high hypoxia inducible factor 1 alpha expression. High CTSA expression was associated with shorter recurrence free interval (RFI) (p=0.0001). In multivariate survival analysis for patients treated with breast conserving surgery, CTSA was an independent predictor of shorter RFI (p=0.015). DCIS associated with IBC showed higher CTSA expression than pure DCIS (p=0.04). In the DCIS/IBC cohort, CTSA expression was higher in the invasive component than DCIS component (p less than 0.0001).
Conclusion: CTSA is not only associated with aggressive behaviour and poor outcome in DCIS but also a potential marker to predict co-existing invasion in DCIS.

Citation

Toss, M. S., Miligy, I. M., Haj-Ahmad, R., Gorringe, K. L., AlKawaz, A., Mittal, K., …Rakha, E. A. (2019). The prognostic significance of lysosomal protective protein (Cathepsin A) in breast ductal carcinoma in situ. Histopathology, 74(7), 1025-1035. https://doi.org/10.1111/his.13835

• Journal Article Type: Article
• Acceptance Date: Feb 3, 2019
• Online Publication Date: Feb 6, 2019
• Publication Date: Feb 6, 2019
• Deposit Date: Feb 8, 2019
• Publicly Available Date: Feb 7, 2020
• Journal: Histopathology
• Print ISSN: 0309-0167
• Electronic ISSN: 1365-2559
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 74
• Issue: 7
• Pages: 1025-1035
• DOI: https://doi.org/10.1111/his.13835
• Keywords: DCIS; proteolytic; CTSA; recurrence
• Public URL: https://nottingham-repository.worktribe.com/output/1527834
• Publisher URL: https://onlinelibrary.wiley.com/doi/abs/10.1111/his.13835
• Contract Date: Feb 8, 2019