Cathepsins B and L are markers for clinically invasive types of meningiomas.

OBJECTIVE: Meningiomas are benign neoplasms that derive from coverings of the brain. Approximately 10% of benign tumors progress into atypical, malignant tumors, thus constituting a subset of histopathologically benign tumors that are clinically invasive. The aim of this study was to evaluate cathepsins B and L and their inhibitors as new prognostic factors that could distinguish malignant from benign forms of meningiomas. METHODS: Using immunohistochemical analysis and specific monoclonal antibodies, we evaluated the levels of cathepsins B and L and the levels of the endogenous cysteine proteinase inhibitors stefin A and cystatin C in 88 meningiomas. Immunohistochemical scores were determined as the sum of the frequency (0-3) and intensity (0-3) of immunolabeling of the tumor cells. RESULTS: Of the 88 tumors studied, 67 were benign meningiomas and 21 were atypical meningiomas. Among the benign group, nine tumors had certain features of malignancy. These tumors were classified as border benign meningiomas, and the rest were classified as clear benign meningiomas. A high immunohistochemical score (4-6) for cathepsin B was more frequent in atypical tumors than in clear benign tumors (P < 0.001). Compared with clear benign tumors, higher cathepsin B immunohistochemical scores were found in atypical tumors (P < 0.001) and border benign tumors (P < 0.03). No statistical difference in immunohistochemical staining of cathepsin B was found between atypical meningiomas and border benign meningiomas. Higher expression of cathepsin L was found in atypical tumors as compared with clear benign tumors (P < 0.03), but it was not observed in border benign as compared with clear benign meningiomas. No immunostaining for stefin A and cystatin C was detected in any of the tumors. CONCLUSION: We show that the levels of cathepsin B and cathepsin L antigens are significantly higher in invasive types of benign meningioma. Specifically, cathepsin B may be used as a diagnostic marker to distinguish histomorphologically benign but invasive meningiomas from histomorphologically clear benign tumors.

Measurement of the lateral recess angle as a possible alternative for evaluation of the lateral recess stenosis on a CT scan.

Stenosis of the lateral recess in the lumbar spinal canal is a clinical problem, especially in terms of surgical management. Criteria for the diagnosis and surgical treatment of lateral recess stenosis (LRS) are not clearly defined. Several authors have suggested measurement of the lateral recess height (LRH) on computed tomography (CT) scans as a helpful tool for making decisions in regard of management. The present study is based on the assumption that measurement of the lateral recess angle (LRA) may be useful in the clinical management of lateral recess stenosis. The reliability and significance of the results have been analyzed. In 35 patients, the stenosis was confirmed by intraoperative measurement of the lateral recess height. Fifty-three affected lateral recesses were analyzed. Before surgery, the heights on CT scans were measured. The mean value was 3.3 mm (SD = 0.9 mm), while 41 of them were 3.6 mm or less. Furthermore, the angles on CT scans were evaluated. The mean value was 25.9 degrees (SD = 4.9 degrees), 48 of them were 30 degrees or less and only 5 of them achieved more than 30 degrees. Results reveal that the best quantitative determination of a lateral recess stenosis is a CT scan angle measurement with a critical value of 30 degrees. A CT scan height of 3.6 mm or less is also indicative of stenosis. Statistical evaluation of the data by multiple regression analysis revealed agreement between intraoperative findings and measured heights (p = 0.02), while even better results were noted for angles (p < 0.01). Interfacet distance (IF) was found to be least predictive (p = 0.04).

Cathepsin B and its inhibitor stefin A in brain tumors.

Cysteine protease cathepsin B (CatB) and its endogenous inhibitor stefin A (StA) play an important role in tumor progression. Increase of CatB expression and lower levels of its inhibitors were associated with tumor malignancy in brain tumors. In this study of 100 patients, CatB was localized by immunostaining to both, tumor and endothelial cells of primary brain tissue. Significant correlation with poor prognosis was found by univariate Cox's regression model. Intense overall immunostaining and immunostaining in endothelial cells alone were prognostic for survival (p=0.003 in both). When comparing CatB expression at mRNA level, we found considerable differences between center and periphery of a tumor as well as between different tumor samples. StA mRNA was only detected in benign, but not in malignant tissues. We suggest that screening of cysteine-protease genes expression can be applied in clinical prognosis of brain tumors.

Cathepsin B immunohistochemical staining in tumor and endothelial cells is a new prognostic factor for survival in patients with brain tumors.

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.