Expression of Cathepsin D in early-stage breast cancer and its prognostic and predictive value

Alhudiri, Inas; Nolan, Christopher; Ellis, Ian; Elzagheid, Adam; Green, Andrew; Chapman, Caroline

Abstract

Purpose
Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. There are conflicting results regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. This study aimed to evaluate the expression and prognostic significance of Cathepsin D in early-stage breast cancer.

Methods
Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n = 954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of Cathepsin D expression with clinicopathological parameters and prognosis was evaluated.

Results
Cathepsin D expression was positive in 71.2% (679/954) of breast cancer tumours. Positive expression of Cathepsin D was significantly associated with high histological grade (p = 0.007), pleomorphism (p = 0.002), poor Nottingham Prognostic Index (NPI) score (p < 0.002), recurrence (p = 0.005) and distant metastasis (p < 0.0001). Kaplan–Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer-specific survival (p = 0.001), higher risk of recurrence (p = 0.001) and distant metastasis (p < 0.0001). ER-positive tumours expressing Cathepsin D and treated with tamoxifen demonstrated a significantly higher risk of distant metastasis.

Conclusion
Cathepsin D expression significantly predicts poor prognosis in breast cancer and is associated with variables of poor prognosis and shorter outcome. The strong association of Cathepsin D with aggressive tumour characteristics and poor outcomes warrants further research of its potential as a therapeutic target The results also suggest a possible interaction between Cathepsin D and tamoxifen therapy in ER-positive breast cancer which needs further investigation to elucidate the underlying mechanisms.

• Journal Article Type: Article
• Acceptance Date: Feb 8, 2024
• Online Publication Date: Apr 5, 2024
• Publication Date: 2024-07
• Deposit Date: Mar 19, 2024
• Publicly Available Date: Apr 6, 2025
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 206
• Issue: 1
• Pages: 143-153
• DOI: https://doi.org/10.1007/s10549-024-07293-y
• Keywords: Breast cancer; Cathepsin D; immunohistochemistry; tissue microarray; prognosis
• Public URL: https://nottingham-repository.worktribe.com/output/32741997
• Publisher URL: https://link.springer.com/article/10.1007/s10549-024-07293-y