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Ex Vivo Culture of Circulating Tumor Cells in the Cerebral Spinal Fluid from Melanoma Patients to Study Melanoma-Associated Leptomeningeal Disease
Published on: March 29, 2024
Matrix metalloprotease-9 in cerebrospinal fluid correlates with disease activity in lymphomatous meningitis
Eric T Wong1, Diana Lee, Angela Tam
1Brain Tumor Center & Neuro-Oncology Unit, Harvard Medical School & Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. ewong@bidmc.harvard.edu
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/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).
Conclusion:
Matrix metalloprotease-9 correlated strongly with lymphomatous meningitis, but MMP-2, activated MMP-2, activated MMP-9, and 130-kDa MMP did not.
Insights
Matrix metalloprotease-9 (MMP-9) levels in cerebrospinal fluid strongly correlate with lymphomatous meningitis. This biomarker shows promise for diagnosing this challenging condition, unlike other MMPs tested.
Area of Science:
- Neuro-oncology
- Biochemistry
- Diagnostic biomarkers
Background:
- Diagnosing lymphomatous meningitis via cerebrospinal fluid (CSF) cytology is limited by low sensitivity.
- Matrix metalloproteases (MMPs) are implicated in cancer invasion and angiogenesis, suggesting a role in CNS lymphomas.
Purpose of the Study:
- To investigate the correlation between MMPs in CSF and the diagnosis of lymphomatous meningitis.
- To evaluate MMP-2, MMP-9, activated MMP-9, and 130 kDa MMP as potential biomarkers.
Main Methods:
- Retrospective analysis of 29 CSF samples from 5 patients with primary or metastatic CNS lymphomas.
- Zymography was used to measure MMP levels, correlated with CSF cytology, total protein, and glucose.
Main Results:
- Elevated CSF white blood cells and MMP-9 levels showed a strong correlation with abnormal CSF cytology (P = 0.03 and P = 0.02, respectively).
- Activated MMP-9 levels fluctuated with disease activity, but the correlation with abnormal cytology did not reach statistical significance (P = 0.17).
Conclusions:
- Matrix metalloprotease-9 (MMP-9) is a promising biomarker strongly correlated with lymphomatous meningitis.
- MMP-2, activated MMP-2, activated MMP-9, and 130 kDa MMP were not found to be significantly correlated with the condition.
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