Prognostic value of tumor microinvasion and metalloproteinases expression in intracranial pediatric ependymomas

Ependymomas are common pediatric intracranial neoplasms that often appear well circumscribed on imaging but may recur when they are treated by surgical resection alone. The current World Health Organization histological grading system does not accurately predict clinical behavior. The aim of this study was to identify histological and immunohistochemical features that correlate with clinical course in patients with ependymomas treated by gross total resection. We analyzed 41 pediatric ependymomas for microinvasion and correlated immunostaining for the metalloproteinase (MMP)-2 and MMP14 and for ezrin and bcl-2 with clinical outcome. Gross total resection had a significantly positive effect on overall survival and progression-free survival. In 28 patients who underwent gross total resection, microinvasion correlated with poor overall survival (p = 0.003) and progression-free survival (p = 0.03). Gross totally resected tumors with high expression of MMP2 and MMP14 had significantly shorter overall survival. Ezrin staining identified tumor cells invading the adjacent white matter that were not identified by routine stains, but Ezrin staining and bcl-2 staining did not provide strong prognostic correlations. The data indicate that tumor microinvasion into adjacent brain and tumor expression of MMP2 and MMP14 predict both overall and progression-free survival in pediatric ependymomas, and these are useful prognostic markers that may help stratify patients for adjuvant therapies.