IMMUNOLOCALIZATION OF CATHEPSIN-B IN HUMAN GLIOMA - IMPLICATIONS FOR TUMOR INVASION AND ANGIOGENESIS

The poor prognosis of patients with malignant gliomas is at least part ially due to the invasive nature of these tumors. In this study, the a uthors investigated the possibility that the cysteine protease catheps in B (CB) is a participant in the process of glial tumor cell invasion . To accomplish this, an immunohistochemical analysis was made of the localization of antibodies to CB in biopsies of five specimens of norm al brain, 16 astrocytomas, 33 anaplastic astrocytomas, and 33 glioblas tomas multiforme. Staining was scored according to the percentage of p ositive cells and the intensity of the stain, graded from 0 to 3+. Sta ining for CB was not seen in any of five samples of normal brain excep t for occasional neuronal cell bodies and microglia. Only five (31%) o f 16 astrocytomas showed a small percentage of positive cells (0.01%-3 %) that were stained in a light, diffuse cytoplasmic pattern (1+). Twe nty-nine (87.8%) of 33 anaplastic astrocytomas showed positive light, granular staining in 2% to 40% of cells. In anaplastic astrocytoma, th e staining within a tumor was heterogeneous with intensities of 1+ (17 %), 1+ to 2+ (29%), or 2+ (55%). In contrast, all 33 (100%) glioblasto mas were positive in 10% to 90% of cells. The staining was present in a coarse, granular pattern with an intensity of 2+ (12%) or 3+ (88%). Tumor cells infiltrating into brain adjacent to malignant gliomas stai ned positively in 26 cases that could be evaluated for glioblastoma mu ltiforme; these invading cells frequently followed penetrating blood v essels as typical ''secondary structures of Scherer.'' Moderate to int ense CB staining associated with endothelial proliferation in high-gra de tumors was also observed, especially in regions of tumor infiltrati on into adjacent normal brain. These results provide evidence consiste nt with the hypothesis that CB is functionally significant in the proc ess of tumor invasion and angiogenesis in the clinical progression of the malignant phenotype in astrocytomas.