Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ

Toss, Michael S.; Miligy, Islam M.; Gorringe, Kylie L.; Mittal, Karuna; Green, Andrew R.; Aneja, Ritu; Ellis, Ian O.; Rakha, Emad A.

Abstract

Aims: Cathepsin V (CTSV/CTSL2) is a lysosomal cystine proteinase and plays a role in extracellular matrix degradation. It is associated with poor prognosis in invasive breast cancer (IBC), but its role in breast ductal carcinoma in situ (DCIS) remains unclear. In this study, we aimed to evaluate the prognostic significance of CTSV in DCIS.
Methods: CTSV protein expression was immunohistochemically assessed in a well characterised and annotated cohort of DCIS comprising, pure DCIS (n=776) and DCIS coexisting with IBC (n=239). CTSV expression was analysed in tumour cells and surrounding stroma, including its association with clinicopathological parameters and outcome.
Results: In pure DCIS, high CTSV expression was observed in 29% of epithelial tumour cells and 20% of surrounding stroma. High expression in both components was associated with features of poor prognosis including higher nuclear grade, hormone receptor negativity and HER2 positivity. In addition, stromal CTSV expression was associated with larger DCIS size, comedo type necrosis and high proliferation index. DCIS associated with IBC showed higher CTSV expression than pure DCIS either within the epithelial tumour cells or surrounding stroma (p

Citation

Toss, M. S., Miligy, I. M., Gorringe, K. L., Mittal, K., Green, A. R., Aneja, R., Ellis, I. O., & Rakha, E. A. (2020). Prognostic significance of cathepsin V (CTSV/CTSL2) in breast ductal carcinoma in situ. Journal of Clinical Pathology, 73(2), 76-82. https://doi.org/10.1136/jclinpath-2019-205939

• Journal Article Type: Article
• Acceptance Date: Aug 10, 2019
• Online Publication Date: Aug 23, 2019
• Publication Date: 2020-02
• Deposit Date: Aug 12, 2019
• Journal: Journal of Clinical Pathology
• Print ISSN: 0021-9746
• Electronic ISSN: 1472-4146
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 73
• Issue: 2
• Pages: 76-82
• DOI: https://doi.org/10.1136/jclinpath-2019-205939
• Keywords: DCIS; proteolysis; CTSV; stroma; recurrence
• Public URL: https://nottingham-repository.worktribe.com/output/2419685
• Publisher URL: https://jcp.bmj.com/content/early/2019/08/22/jclinpath-2019-205939
• Additional Information: This article has been accepted for publication in Journal of Clinical Pathology following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/jclinpath-2019-205939 © Authors (or their employer(s))