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

OBJECTIVE: Meningiomas are benign neoplasms that derive from coverings of t he brain. Approximately 10% of benign tumors progress into atypical, malign ant tumors, thus constituting a subset of histopathologically benign tumors that are clinically invasive. The aim of this study was to evaluate cathep sins B and L and their inhibitors as new prognostic factors that could dist inguish malignant from benign forms of meningiomas. METHODS: Using immunohistochemical analysis and specific monoclonal antibod ies, we evaluated the levels of cathepsins B and L and the levels of the en dogenous cysteine proteinase inhibitors stefin A and cystatin C in 88 menin giomas. Immunohistochemical scores were determined as the sum of the freque ncy (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 a typical meningiomas. Among the benign group, nine tumors had certain featur es of malignancy. These tumors were classified as border benign meningiomas , and the rest were classified as clear benign meningiomas. A high immunohi stochemical score (4-6) for cathepsin B was more frequent in atypical tumor s than in clear benign tumors (P < 0.001). Compared with clear benign tumor s, higher cathepsin 8 immunohistochemical scores were found in atypical tum ors (P < 0.001) and border benign tumors (P < 0.03). No statistical differe nce in immunohistochemical staining of cathepsin B was found between atypic al meningiomas and border benign meningiomas. Higher expression of cathepsi n 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 beni gn 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. Specifica lly, cathepsin B may be used as a diagnostic marker to distinguish histomor phologically benign but invasive meningiomas from histomorphologically clea r benign tumors.