DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas

Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor. The prognosis for children harboring this lesion remains largely unpredictable. Assessment of histologic features alone only provides a marginal insight into the biologic behavior of these lesions. Hence, the identification of novel molecular markers capable of characterizing these lesions more accurately with respect to their biologic aggressiveness is definitely needed. Our current study examined the expression of nuclear DNA topoisomerase IIalpha (TIIalpha), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs. TIIalpha expression was found to extend over a wide range in the study cohort (3.9-69.1%). A cutoff labeling index of 12% was found to define 2 prognostic subgroups (TIIalpha <12 vs. >or=12) with profoundly different 5-year progression-free survival (60% vs. 8%; p = 0.0108, log-rank test) and overall survival (100% vs. 8%; p = 0.0038) rates. TIIalpha expression was significantly linked to MIB-1 antibody labeling of the Ki-67 nuclear antigen (R = 0.919, p < 0.001). A high TIIalpha labeling index remained associated with short progression-free survival (p = 0.022) and overall survival (p = 0.022) in multivariate analysis (Cox regression). In conclusion, considering that TIIalpha expression was not related to histopathologic grade, biological characteristics as assessed by TIIalpha labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.