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.


CONCLUSIONS
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.
Department of Neurosurgery, Maribor Teaching Hospital, Ljubljanska, Slovenia. tadej.strojnik@siol.net
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Zidanik
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Kos
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Lah
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002401:Cathepsin B / Q000032:analysis* / Q000037:antagonists & inhibitors; D056668:Cathepsin L; D002403:Cathepsins / Q000032:analysis* / Q000037:antagonists & inhibitors; D002556:Cerebrospinal Fluid Proteins / Q000494:pharmacology; D055312:Cystatin A; D055316:Cystatin C; D015891:Cystatins / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000737:chemistry* / Q000473:pathology*; D008579:Meningioma / Q000737:chemistry* / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis
D014408:Biomarkers, Tumor; C525030:CST3 protein, human; D002556:Cerebrospinal Fluid Proteins; D055312:Cystatin A; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; C026407:CSTA protein, human; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L