PROGNOSTIC-SIGNIFICANCE OF CATHEPSIN-B AND CATHEPSIN-L IN PRIMARY HUMAN BREAST-CANCER

Purpose: Evaluation of the clinical significance of cytosolic tumor le vels of the lysosomal cysteine proteases cathepsin B (catB) and cathep sin L (catL) in patients with primary breast cancer. Patients and Meth ods: Cats (n = 1,500) and catL (n = 1,391) levels were determined by e nzyme-linked immunosorbent assay (ELISA) in cytosols routinely prepare d from frozen-tissue samples that were submitted to our laboratory for the assessment of steroid-hormone-receptor status. The median duratio n of follow-up of patients still alive at the time of analysis was 93 months. Results: Relating cats and catL levels with classical prognost ic factors, the proteases were positively correlated with the number o f positive lymph nodes (P < .01), and negatively with the level of ste roid-hormone receptors (P < .01). We did not find a significant relati onship between cats or catL levels with age and menopausal status of t he patients or with the size of the primary tumor. The levels of cats and catL were positively correlated with each other and with the rates of relapse and death (all, p < .0001). In multivariate regression ana lysis for relapse-free survival (RFS) and overall survival (OS), corre cted for the contribution of age/menopausal status, tumor size, the nu mber of positive lymph nodes, and steroid-hormone-receptor status, cat s and catL were significant predictors of the rates of relapse and dea th (all, P < .01). No statistically significant interactions of cats o r catL with any of the classical prognostic factors or with each other were observed in their associations with the rates of relapse and dea th. Conclusion: CatB and catL levels measured in routinely prepared cy tosols are strong parameters to predict the rate of relapse and the le ngth of survival after treatment of the primary breast tumor. (C) 1998 by American Society of Clinical Oncology.