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Prognostic significance of an apoptotic index and apoptosis/proliferation ratio for patients with high-grade astrocytomas

The Preuss Laboratory for Molecular Neuro-Oncology, Brain Tumor Research Center (H.K., N.K., M.A.I.); Department of Neurological Surgery, University of California, San Francisco, CA 94143 (H.K., K.R.L., N.K., M.A.I.); Mayo Clinic and Foundation, Rochester, MN 55905 (J.R.O., N.I., T.S., B.W.S., J.C.B., R.B.J.); Toledo Community Hospital Oncology Program, Toledo, OH 43623 (P.L.S.)

² Address correspondence and reprint requests to Mark A. Israel, Norris Cotton Cancer Center, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, 1 Medical Center Dr., Lebanon, NH 03756.

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.

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