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

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

doi:10.1007/s10549-024-07293-y

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

Breast Cancer Res Treat. 2024 Apr 5. doi: 10.1007/s10549-024-07293-y. Online ahead of print.

Authors

Inas Alhudiri^{1

2}, Christopher Nolan¹, Ian Ellis¹, Adam Elzagheid², Andrew Green³, Caroline Chapman⁴

Affiliations

¹ Breast Pathology Research Group, Nottingham Breast Cancer Research Centre, Biodiscovery Institute, Faculty of Medicine, The University of Nottingham, Nottingham, UK.
² Genetic Engineering Department, Libyan Biotechnology Research Centre, Tripoli, Libya.
³ Breast Pathology Research Group, Nottingham Breast Cancer Research Centre, Biodiscovery Institute, Faculty of Medicine, The University of Nottingham, Nottingham, UK. andrew.green@nottingham.ac.uk.
⁴ Eastern Bowel Cancer Screening Hub, Nottingham University Hospitals, NHS Trust, Nottingham, UK.

PMID: 38578521
DOI: 10.1007/s10549-024-07293-y

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.

Keywords: Breast cancer; Cathepsin D; Immunohistochemistry; Prognosis; Tissue microarray.