title: Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas.
abstract: We evaluated the association of spontaneous apoptosis and an apoptosis/proliferation index with survival to determine the potential of such measures to serve as predictive markers for patients with glioblastoma multiforme (GBM). We examined the extent of spontaneous apoptosis in tumors from newly diagnosed patients, 75 with GBM and 21 with anaplastic astrocytoma, who were entered on treatment protocols of the North Central Cancer Treatment Group. In the group of GBM patients, those with a higher apoptotic index tended to live longer ( P = 0.04; Cox proportional hazards model including performance score, age, and extent of resection in a multivariate model). We found that the apoptotic index values for anaplastic astrocytoma patients tended to be lower than those in the GBM patients, although with small sample sizes, the result was not statistically significant ( P = 0.1). We also examined expression of the Ki-67 cell proliferation antigen immunohistochemically using the MIB-1 monoclonal antibody. Ki-67 expression did not provide additional information regarding the survival of patients with GBM. In this group of GBM patients, those patients with higher apoptotic index/proliferation ratios had a better prognosis than did those with a low ratio ( P < 0.021, same model as above). These findings suggest that both apoptosis and a cell death/cell proliferation ratio are associated with patient survival, and they may be useful for either the clinical evaluation of patients with GBM or the stratification of patients for treatment evaluation.
authors.affiliation: The Preuss Laboratory for Molecular Neuro-Oncology, Brain Tumor Research Center, University of California-San Francisco, San Francisco, CA 94143, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kuriyama
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: Judith R
authors.initials: JR
authors.lastname: O'Fallon
authors.forename: N
authors.initials: N
authors.lastname: Iturria
authors.forename: Thomas
authors.initials: T
authors.lastname: Sebo
authors.forename: Paul L
authors.initials: PL
authors.lastname: Schaefer
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Scheithauer
authors.forename: Jan C
authors.initials: JC
authors.lastname: Buckner
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.forename: Mark A
authors.initials: MA
authors.lastname: Israel
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001254:Astrocytoma / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D015415:Biomarkers; D001932:Brain Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D002455:Cell Division; D005260:Female; D005909:Glioblastoma / Q000737:chemistry / Q000401:mortality / Q000473:pathology*; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins