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Cathepsin B, a Prognostic Indicator in Lymph Node-negative Breast Carcinoma Patients: Comparison with Cathepsin D, Cathepsin L, and Other Clinical Indicators¹

Tamara T. Lah², Miha erek, Andrej Blejec, Janko Kos, Ella Gorodetsky, Robert Somers and Ierachmiel Daskal

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia [T. T. L., M. C., A. B.]; Department of Biochemical Research and Drug Design, KRKA, d.d. Novo mesto, 8000 Slovenia [J. K.]; and Breast Cancer Center [R. G. S.] and Department of Pathology and Laboratory Medicine [E. G., I. D.], Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141

New prognosticators are needed for breast cancer patients after the initial surgical treatment to make therapeutic decisions that ultimately will affect their DFS. These consist of specific proteolytic enzymes including lysosomal endopeptidases. In this study, the activity and protein concentrations of cathepsins (Cats) D, B, and L were measured in 282 invasive breast tumor cytosols. These potential biological prognostic indicators were compared with other histopathological parameters, such as tumor size, lymph node involvement, tumor-node-metastasis stage, histological grade, DNA analysis, and steroid receptors. CatD protein concentration correlated with lymph node involvement. CatB and CatL levels correlated significantly with Scarf-Bloom-Richardson histological grade and were also higher in estrogen-negative tumors, and CatB was higher in larger tumors.

As prognostic markers, CatB concentration was significant for increased risk for recurrence in the entire patient population and specifically also in lymph node-negative patients as follows: high CatB concentration (above 371 µg/g) in tumor cytosols was significant (P < 0.00) for high risk of recurrence but was of only borderline prognostic significance (P < 0.06) for overall survival of all patients. In lymph node-negative patients, CatB (above 240 µg/g, P < 0.003) was highly significant for recurrence-free survival, followed by CatL (above 20 µg/g, P < 0.049) and CatD (above 45 nmol/g, P < 0.044) concentrations. For overall survival of node-negative patients, only CatB was a significant (P < 0.014) prognosticator. We conclude that CatB is useful as a prognostic indicator in lymph node-negative patients. This suggests that selective adjuvant therapy should be applied in this lower risk group of patients when high levels of CatB are determined.

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