Matrix Metalloproteinasi-9: emergente biomarcatore nei meningiomi?

Introduction The WHO classification remains the gold standard mean to diagnose and to prognosticate meningioma patients outcome, even if this tool is not always reliable in predicting tumor evolution. Identification of new markers, preferentially detectable in non-invasive and inexpensive manner, remains one of the most difficult issue needing to be solved. Several studies identified matrix-metalloproteases 9 (MMP-9) as a key molecule in brain cancer development, since its ability to activate cytokines and growth factors which are essential in tumor microenvironment maintenance and also in tumor invasion and metastatic processes. Thus, it shows interesting biomarker potential. Materials and Methods In this unicentre observational study we evaluated, by substrate zymography, serum levels of MMP-9 in a cohort of 28 meningioma patients (16 grade I and 12 grade II). The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. In parallel, by immunohistochemestry, we analyzed MMP-9, Ki67 and Progesteron Receptor (PR) levels in tissue samples from the same patients. Results Zymography showed that MMP-9 monomeric (92kDa) and multimeric (240kDa) forms lytic activities are significantly higher in meningioma specimens compared to healthy controls (p<0.001), despite no relevant differences have been observed between grade I and grade II meningiomas. In contrast, MMP-9 immunohistochemical analysis revealed that MMP-9 cytoplasmic reactivity is significantly increase in atypical meningiomas compared with low-grade ones (p=0.036). Moreover, a positive correlation between MMP-9 percentage and Ki-67 (Sperman Rho coefficient r=0.418 and p=0.034) have been underlined. Conclusion Although the sample size is small for conclusion to be drawn and further investigations are needed for a better determination of diagnostic/prognostic value of MMP-9, our study suggests that evaluation of serum and tissue MMP-9 might provide clinicians additional objective information for improving meningioma patient management.