Matrix Metalloprotease–9 in Cerebrospinal Fluid Correlates with Disease Activity in Lymphomatous Meningitis

Purpose:The detection of lymphoma cells in cerebrospinal fluid (CSF) as a means to diagnose lymphomatous meningitis is problematic due to its low sensitivity. We hypothesize that matrix metalloproteases (MMPs) would be important in lymphomatous meningitis because lymphoma cells may produce MMPs for brain invasion and angiogenesis.Patients and Methods:Twentynine samples of CSF collected longitudinally from 5 patients receiving treatments for primary or metastatic CNS lymphomas were retrospectively analyzed by zymography. Cerebrospinal fluid cytology was correlated with levels of total protein, glucose, MMP-2, MMP-9, activated MMP-9, and 130 kDa MMP.Results:Increased CSF white blood cells (65 ± 32 cells/μL vs. 9 ± 8 cells/μL; P = 0.03) and MMP-9 (12.108 ± 2.675 vs. 9.359 ± 1.936; P = 0.02) had a strong correlation with abnormal CSF cytology. In addition, we observed that activated MMP-9 would appear and disappear depending on disease activity. Although there was nearly a 4-fold increase of mean activated MMP-9 in CSF samples with abnormal cytology findings when compared with negative cytology findings, the correlation did not reach statistical significance (1.382 ± 0.76 vs. 0.389 ± 0.155; P = 0.17).Conclusion:Matrix metalloprotease–9 correlated strongly with lymphomatous meningitis, but MMP-2, activated MMP-2, activated MMP-9, and 130-kDa MMP did not.