Prognostic significance of c-met expression in glioblastomas

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Purpose: We investigated whether the expression of c-Met protein in glioblastomas was associated with overall survival and biological features representing tumor invasiveness.
 Experimental Design: Paraffin-embedded specimens of glioblastomas from 62 patients were assessed by immunohistochemical (IHC) analysis of c-Met expression. Furthermore, we investigated the methylation status of MGMT using methylation-specific PCR, matrix metalloproteinase (MMP) -2, -9, and associated oncogenes using immunohistochemical study. Patients’ clinical data were used to analyze the association between c-Met expression and clinico-biological features representing tumor invasiveness on the uni- and multi-variate analyses.
 Results: C-Met overexpression was detected in 33.9% (21/62) of glioblastomas. In patients with tumors overexpressing c-Met, median survival time was 10.7 months (95% CI: 9.3-12.0 months), compared with a median survival time of 20.0 months (95% CI: 13.5-26.5 months) for patients whose tumors expressed little or no c-Met (P < .001). In the radiographic analysis, tumors from 9 of 21 patients (42.9%) with c-Met overexpression demonstrated invasive and multifocal lesions on the initial magnetic resonance images, whereas tumors from only 7 of 41 patients (17.1%) with no or little c-Met expression showed these features (P = .036). We also found a significant association between c-Met expression and the expression of MMP-2 and -9 (P = .032 and P = .029, respectively). Furthermore, c-Myc overexpression was closely correlated with c-Met overexpression on the IHC (P = .002).
 Conclusions: C-Met overexpression appears to be associated with shorter survival time and poor treatment response in GBM patients. We suggest that an increase of tumor invasiveness by c-Met can account for this poor clinical outcome. This implies that more effective therapeutic strategies targeting the c-Met receptor may have important clinical implications.