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Aberrant p53, mdm2, and Proliferation Differ in Glioblastomas from Long-Term Compared with Typical Survivors¹

Departments of Pathology [J. O., J. U. L., K. D. A.] and Neurological Surgery [E. C. B., K. R. L., M. P., M. B.], University of California, San Francisco, San Francisco, California 94143; Department of Medicine, Tom Baker Cancer Center University of Calgary, Calgary, Alberta, Canada 2N4N2 [P. F., J. S.]; and Departments of Laboratory Genetics [S. P., R. J.] and Neurology [J. U., B. P. O.], Mayo Clinic and Foundation, Rochester, Minnesota 55905

Purpose: Glioblastoma multiforme (GBM) is a highly lethal neoplasm with a median survival of 1 year. Only 2–5% of patients originally diagnosed with GBM will survive 3 years. Whether tumors from these long-term survivors (LTSs) exhibit molecular genetic differences compared with typical GBM survivors is not known.

Experimental design: Tumors from 41 patients initially diagnosed with GBM and having survival 3 years (LTS) was compared with 48 GBMs from short-term survivors (STSs, survival 1.5 years) for p53 aberrations (expression/mutation), epidermal growth factor receptor overexpression, mdm2 overexpression, and proliferation index.

Results: Nuclear p53 expression was significantly more frequent in the LTS group. However, no difference in the rate of p53 mutation was evident. Overexpression of epidermal growth factor receptor was slightly more frequent in the STS patients, but this is not statistically different. mdm2 overexpression was significantly more frequent in the STSs, and this group had a significantly higher median proliferation index.

Conclusion: Long-term GBM survivors were more likely to have p53-overexpressing tumors, although a difference in p53 mutation rate could not be detected. They were less likely to exhibit mdm2 overexpression and had a lower proliferation rate compared with typical GBM survivors.

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