Cells producing cathepsins D, B, and L in human breast carcinoma and theirassociation with prognosis

Lysosomal proteinases, cathepsins D, B, and L have been associated with mal ignant tumor progression and with prognosis in various human carcinomas. In the current study, the immunohistochemical localization of cathepsins in t umor cells was correlated with cathepsin protein concentration in breast ca rcinoma cytosols from 77 patients. Significant correlation was found for ca thepsin D (P < .041) and borderline correlation for cathepsin B (P < .055) but not for cathepsin L. We hypothesize that the poor correlation of cystei ne cathepsins was attributable to the fact that they were present not only in malignant epithelial cells, but also in infiltrating macrophages and str omal fibroblasts. In addition, tumor-surrounding myoepithelial cells (42% o f tumors) and myofibroblasts (26% of tumors) as well as endothelial cells o f neovasculature (10% of tumors) all stained specifically for cathepsin B. Two thirds of tumors co-expressed cathepsins B and L in tumor cells, wherea s only 17% of tumors co-expressed all 3 cathepsins. Intense immunostaining for cathepsin D of tumor cells was observed in tumors at high TNM stage and tumors having positive lymph nodes. The expression of cathepsin B was inde pendent of established prognostic factors, whereas intense cathepsin L stai ning in tumor cells was associated with high histological grade. With respe ct to prognosis of patient survival, only tumor-cell-associated cathepsin D (P = .042) and myoepithelial cell-associated cathepsin B (P = .061) showed borderline significance. Cathepsins B and L immunostaining in tumor cells was not prognostic. In contrast, cytosolic levels of cathepsin B correlated with higher rate of relapse. Taken together, these results show the divers ity in the cellular distribution of cathepsins in human breast carcinoma, p resumably reflecting specific regulation and function of each of the cathep sins during tumor progression. Copyright (C) 2000 by W.B. Saunders Company.