title: Expression of Ki-67, topoisomerase IIalpha and c-MYC in astrocytic tumors: correlation with the histopathological grade and proliferative status.
abstract: 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.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. mariofaria@doctor.com
authors.forename: Mário H G
authors.initials: MH
authors.lastname: Faria
authors.forename: Bronner P A
authors.initials: BP
authors.lastname: Gonçalves
authors.forename: Régia M do S V
authors.initials: RM
authors.lastname: do Patrocínio
authors.forename: Manoel O
authors.initials: MO
authors.lastname: de Moraes-Filho
authors.forename: Silvia H B
authors.initials: SH
authors.lastname: Rabenhorst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D016271:Proto-Oncogene Proteins c-myc; D004250:DNA Topoisomerases, Type II