A comparison of the pattern of cathepsin-D expression in fibroadenoma, fibrocystic disease, preinvasive and invasive ductal breast carcinoma

Abstract

In the metastatic process, proteolytic enzymes play an important role in mediating the passage of cancer cells through the basement membrane and extracellular matrix. We have compared cathepsin-D (CD) expression in a range of benign and malignant breast lesions so as to investigate its role in breast cancer progression. One hundred and sixty-two breast samples, comprising 18 fibroadenomas, 22 fibrocystic disease, 96 invasive ductal carcinoma and 26 lesions with intraductal carcinoma components, were evaluated for CD expression by the standard avidin-biotin-immunoperoxidase complex method on formalin-fixed, paraffin-embedded histological sections using a commercial antibody against human cathepsin-D. Of the invasive ductal carcinomas, 61.5% showed stromal cell CD positivity, whereas 48.9% expressed CD positivity in neoplastic cells. There was significant correlation between neoplastic cell and stromal CD positivity. The prevalences of CD positivity in both neoplastic and stromal cell components were significantly higher (P < 0.05 and P < 0.01, respectively) in histological grade III tumors compared to grades I and II carcinomas. CD expression by either neoplastic or stromal cells did not show significant correlation with patient age and tumor size. Only 15% of intraductal carcinomas were CD positive and expression was limited to neoplastic cells. Neither epithelial nor stromal cells in fibrocystic lesions and fibroadenomas were CD positive, but a weak to moderate positivity was observed within myoepithelial cells in mammary ducts. These findings provide insights into the mechanism whereby tumors with high histological grade mediate invasion into tissue. The role of stromal cells in tumor progression and the means of their recruitment deserve further study.