Immunohistochemical markers for intracranial ependymoma recurrence. An analysis of 88 cases

Intracranial ependymomas are the third most common primary brain tumor in children. Although clinical and histological criteria for ependymoma prognosis are recognized, studies have reported contradictory results. Prognostic significance based on immunohistochemistry of ependymomas has been reported in a few studies. Eighty-eight patients with intracranial ependymomas were examined retrospectively for immunoexpression of various tumor-associated antigens and apoptosis. The results demonstrated significant preponderance of expression of the tenascin, vascular endothelial growth factor protein (VEGF), epidermal growth factor (EGFR), and p53 protein in high-grade tumors. Also high-grade ependymomas revealed more prominent labeling indices (LI) for proliferative marker Ki-S1 and lower LI for cyclin-dependent kinase inhibitor p27/Kip1. For low-grade ependymomas the progression free survival time (PFS) was found to be significantly shorter for Ki-S1 LI>/=5%, and for tenascin, VEGF, and EGFR positivity. For high-grade ependymomas PFS was found to be significantly reduced for age <16 years, subtotal tumor removal, p27 LI <20%, p53 positivity, and for apoptotic index (AI) <1%. The classification regression tree analysis exhibited four groups of ependymomas; (1) low-grade tenascin negative (32 cases, recurrence rate=0), (2) high-grade with AI >/=1% (21 cases, recurrence rate=57%), (3) low-grade tenascin-positive (10 cases, recurrence rate=89%), and (4) high-grade with AI <1% (25 cases, recurrence rate=100%). So, the immunohistochemical variables were found to be strongest predictors of ependymoma recurrence and they seem to be useful for assessing individual tumor prognosis in routinely processed biopsy specimen.