Expression of Ki-67, topoisomerase IIalpha and c-MYC in astrocytic tumors: correlation with the histopathological grade and proliferative status.

Astrocytomas represent the most frequent primary tumors of the central nervous system. Recently, the determination of the proliferative index of astrocytic tumors by different methods has been proposed as a valuable tool for tumor grading and also as a prognostic marker. The aim of the present study was to evaluate the expression of cell proliferation-related proteins in human astrocytic tumors of different histopathological grades (WHO). An immunohistochemical study of the Ki-67, Topoisomerase IIalpha (Topo IIalpha) and c-MYC proteins using the avidin-biotin-peroxidase method was performed in 55 astrocytomas (13 grade I, 14 grade II, 7 grade III and 21 grade IV) and five samples of non-tumor brain tissue (control group). Ki-67, Topo IIalpha and c-MYC positive indices tended to increase according to malignant progression, were absent in non-tumor brain tissue and showed maximum values in high-grade astrocytomas (III and IV). A gradual increase in Ki-67 antigen expression was observed in agreement with mitotic index and histopathological classification. The same was not observed for Topo IIalpha and c-MYC. Ki-67 antigen detection in more than 8.0% of the tumor cells distinguished astrocytoma grade IV, while a labeling index between 1.5 and 8.0% characterized astrocytomas grade III and values below 1.5% discriminated low-grade tumors (I and II). These results indicate that Topo IIalpha and c-MYC expression is associated with cell proliferation in astrocytomas, although not in an exclusive way. Moreover, Ki-67 antigen was found to be the best marker of cellular proliferation, and its expression predicts the grade of astrocytic tumors.