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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.

Authors

Michael S. Toss

Islam M. Miligy

Rita Haj-Ahmad

Kylie L. Gorringe

Abdulbaqi AlKawaz

Karuna Mittal

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



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.

Journal Article Type Article
Publication Date Feb 6, 2019
Journal Histopathology
Print ISSN 0309-0167
Electronic ISSN 1365-2559
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 74
Issue 7
Pages 1025-1035
APA6 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
DOI https://doi.org/10.1111/his.13835
Keywords DCIS; proteolytic; CTSA; recurrence
Publisher URL https://onlinelibrary.wiley.com/doi/abs/10.1111/his.13835

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