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Cathepsin B Immunohistochemical Staining in Tumor and Endothelial Cells Is a New Prognostic Factor for Survival in Patients with Brain Tumors¹

Tadej Strojnik², Janko Kos, Boris idanik, Rastko Golouh and Tamara Lah

Departments of Neurosurgery [T. S.] and Pathology [B. .], Maribor Teaching Hospital, Ljubljanska 5, Maribor 2000, Slovenia; Department of Biochemistry and Molecular Biology, Joef Stefan Institute, Jamova 39, Ljubljana, Slovenia [J. K.]; Department of Biochemical Research and Drug Design, KRKA, d.d., Ljubljana, Slovenia [J. K.]; Department of Pathology, Institute of Oncology, Zaloka 2, 1001 Ljubljana, Slovenia [R. G.]; and National Institute of Biology, Laboratory for Molecular Biology and Biochemistry, Vena pot 111, Ljubljana 1000, Slovenia [T. L.]

The cysteine endopeptidase, cathepsin (Cat) B, and its endogenous inhibitor, stefin A, were found relevant for cancer progression of many neoplasms, including human brain tumors. Histological sections of 100 primary brain tumors, 27 benign and 73 malignant, were stained immunohistochemically for Cat B and stefin A. The immunohistochemical staining of Cat B in tumor cells, endothelial cells, and macrophages was scored separately from 0–12. The score in tumor and endothelial cells was significantly higher in malignant tumors compared with benign tumors (P <0.000). A significant correlation between immunostaining of Cat B (scored together for tumor and endothelial cells) and clinical parameters, such as duration of symptoms, Karnofsky score, psycho-organic symptoms, and histological score was demonstrated. Univariate survival analysis indicated that total Cat B score above 8 was a significant predictor for shorter overall survival (P = 0.003). In glioblastoma multiforme, intense Cat B staining of endothelial cells was a significant predictor for shorter survival (P = 0.003). Stefin A immunostaining was weak and detected only in a few benign and some malignant tumors, suggesting that this inhibitor alone is not sufficient in balancing proteolytic activity of Cat B. We conclude that specific immunostaining of Cat B in tumor and endothelial cells can be used to predict the risk of death in patients with primary tumors of the central nervous system.

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