P53 stratification reveals the prognostic utility of matrix metalloproteinase-9 protein expression in glioblastoma

Background: Despite the conventional acceptance of the matrix metalloproteinases (MMP)-2 and MMP-9, as markers of invasion in glioblastoma (GBM), there is no large body of evidence supporting their role as prognostic markers. Since the co-expression of MMPs with p53 was noted to be prognostic in other cancers, we evaluated the protein expression of MMP-2 and MMP-9 in GBM and explored their prognostic relevance with respect to p53 expression. Materials and Methods: Tumor tissues from a uniformly treated cohort of 132 GBM patients were examined for MMP-2, MMP-9, and p53 protein expression by immunohistochemistry (IHC). Survival analyses were performed by Cox-regression and Kaplan-Meier (KM) survival analysis. P53 IHC-based stratification of all GBM cases was performed, and subgroup-specific expression of MMP-2 and MMP-9 was correlated with survival. Results: MMP-2 and MMP-9 were expressed in p53 positive as well as p53 negative GBM tumors. MMP-2 and MMP-9 protein expressions had no correlation with prognosis. MMP-9 expression, however, emerged as a strong independent predictor of poor survival in p53 positive GBMs on both Cox-regression analysis (P = 0.036) and KM survival analysis (P = 0.008). Further, even on multivariate analysis, MMP-9 remained strongly associated with poor prognosis (P = 0.010). Conclusions: MMP-9 expression strongly associates with poor prognosis in p53 positive GBMs, but the absence of such correlation in p53 negative GBMs, skews the overall relation of this molecule with prognosis. The study highlights that the dual positivity of MMP-9 and p53 is of prognostic relevance in GBM.