Matrix metalloprotease-9 in cerebrospinal fluid correlates with disease activity in lymphomatous meningitis.
OBJECTIVE
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.


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/microL vs. 9 +/- 8 cells/microL; 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).


CONCLUSIONS
Matrix metalloprotease-9 correlated strongly with lymphomatous meningitis, but MMP-2, activated MMP-2, activated MMP-9, and 130-kDa MMP did not.
Wong
Eric T
ET
Brain Tumor Center & Neuro-Oncology Unit, Harvard Medical School & Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ewong@bidmc.harvard.edu
Lee
Diana
D
Tam
Angela
A
Gautam
Shiva
S
Wu
Julian K
JK
D001932:Brain Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D002555:Cerebrospinal Fluid / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D005780:Gelatin; D006801:Humans; D008137:Longitudinal Studies; D008223:Lymphoma / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid*; D008581:Meningitis / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
C015233:gelatin film; D005780:Gelatin; D020780:Matrix Metalloproteinase 9