Immunohistochemical markers for prognosis of ependymal neoplasms

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. One-hundred and twelve 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 apoptotic index (AI), and lower LI for cyclin-dependent kinase inhibitors p27/Kip1 and p14ARF. 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 p27 LI<20%, p14ARF LI<10%, for p53 positivity, and for AI<1%. The CART modeling process exhibited five final groups of ependymoma patients (1) low-grade and tenascin-negative; (2) low-grade and tenascin-positive; (3) high-grade and p53-negative with p14 LI>0%; (4) high-grade with combination of either p53 positivity and p14 LI>10% or p53 negativity and p14 LI<10%; (5) high-grade and p53-positive with p14 LI<10%. In summary, some immunohistochemical variables were found to be the strong predictors of ependymoma recurrence and they seem to be useful for assessing individual tumor prognosis in routinely processed biopsy specimens together with tumor grade. For histologically benign ependymomas immunohistochemical study should be focused on Ki-S1, tenascin, EGFR and VEGF evaluation, whereas p53 expression and number of p27, p14 and ISEL-positive nuclei will be of value in determining PFS from high-grade ependymomas.