Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer

Cathepsins D, B, and L are acidic lysosomal proteinases involved in intracellular protein turnover. Increased levels of these enzymes have been reported to be indicators of aggressive tumor behavior in human and rodent tumors. In breast cancer increased levels of cathepsin D have been reported to be an independent prognostic factor in women with stage I disease. We used standard immunohistochemical techniques on formalin-fixed, paraffin-embedded tissue to examine the levels of cathepsins D, B, and L in 80 carcinomas of the breast and compared that with other indicators of aggressive tumor behavior, including stage of disease, tumor size, nuclear grade, estrogen receptor status, disease recurrence, and 5-year survival rates. Positive granular cytoplasmic staining was detected for cathepsin D in 90% of the tumors, for cathepsin B in two thirds of the tumors, and for cathepsin L in approximately one half of the tumors. Positive staining also was seen in normal breast epithelium, areas of apocrine metaplasia, stromal fibroblasts, and macrophages. Our results did not show a correlation between the expression of cathepsins D, B, and L and other indicators of aggressive tumor behavior. We conclude that the results obtained using polyclonal anticathepsin antibodies do not support the prognostic usefulness of immunohistochemical analysis of these three proteinases in tumor cells in human breast cancer.