title: Prognostic value of survivin and DNA topoisomerase IIα in diffuse and anaplastic astrocytomas.
abstract: Distinguishing WHO grade II astrocytomas from grade III is a difficult task. This study looks into the potential prognostic use of mitotic activity and the proliferation markers Ki67/MiB-1 (Ki67), survivin and DNA topoisomerase IIα (TIIα) in 59 WHO grade II diffuse astrocytomas (DA) and 33 WHO grade III anaplastic astrocytomas (AA), IDH1 R132H-mutated and not otherwise specified (NOS) by means of immunohistochemistry. All proliferation markers showed higher expression in AA compared with DA. Only Ki67 had significantly greater expression in astrocytomas, NOS vs. astrocytomas, IDH1-mutated. Uni-/multivariable COX-regression analyses showed that greater expression of both survivin and TIIα were associated with poorer survival when stratified for IDH1-mutation status and, additionally, achieved hazard rates surpassing clinically established prognostic factors such as age and WHO performance status. Ki67 achieved only statistical significance in univariable analyses, whereas mitoses did not reveal any relation to survival. IDH1-mutated astrocytomas had significantly better survival than astrocytomas, NOS. Among IDH1-mutated astrocytomas no significant difference in survival was shown between DA and AA. Our findings suggest a potential usefulness of proliferation markers in the prognostic setting of astrocytomas independent of IDH1-mutation status, and survivin and TIIα are potential candidates in that regard.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: rosilinv@gmail.com.
authors.forename: R K
authors.initials: RK
authors.lastname: Varughese
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Pathology and Medical Genetics, St Olavs Hospital, Trondheim, Norway.
authors.forename: A J
authors.initials: AJ
authors.lastname: Skjulsvik
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Pathology and Medical Genetics, St Olavs Hospital, Trondheim, Norway.
authors.forename: S H
authors.initials: SH
authors.lastname: Torp
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis*; D001254:Astrocytoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001932:Brain Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000032:analysis / Q000096:biosynthesis*; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D000077022:Survivin; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D004250:DNA Topoisomerases, Type II
keywords: Gliomas; IDH; Immunohistochemistry; Ki67/MiB-1; Prognosis; Survival