© 2002 by Society
© 2002 by the Society forNeuro-Oncology
Prognostic significance of an apoptotic index and apoptosis/proliferationratio 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 ofCalifornia, 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 CommunityHospital Oncology Program, Toledo, OH 43623 (P.L.S.)
2 Address correspondence and reprint requests to Mark A. Israel, Norris CottonCancer Center, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, 1Medical Center Dr., Lebanon, NH 03756.
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Abstract |
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We evaluated the association of spontaneous apoptosis and anapoptosis/proliferation index with survival to determine the potential of suchmeasures to serve as predictive markers for patients with glioblastomamultiforme (GBM). We examined the extent of spontaneous apoptosis in tumorsfrom newly diagnosed patients, 75 with GBM and 21 with anaplastic astrocytoma,who were entered on treatment protocols of the North Central Cancer TreatmentGroup. In the group of GBM patients, those with a higher apoptotic indextended to live longer (P = 0.04; Cox proportional hazards modelincluding performance score, age, and extent of resection in a multivariatemodel). We found that the apoptotic index values for anaplastic astrocytomapatients tended to be lower than those in the GBM patients, although withsmall sample sizes, the result was not statistically significant (P =0.1). We also examined expression of the Ki-67 cell proliferation antigenimmunohistochemically using the MIB-1 monoclonal antibody. Ki-67 expressiondid not provide additional information regarding the survival of patients withGBM. In this group of GBM patients, those patients with higher apoptoticindex/proliferation ratios had a better prognosis than did those with a lowratio (P < 0.021, same model as above). These findings suggestthat both apoptosis and a cell death/cell proliferation ratio are associatedwith patient survival, and they may be useful for either the clinicalevaluation of patients with GBM or the stratification of patients fortreatment evaluation.
Received July 23, 2001; Accepted April 2, 2002
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