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Accumulation of Wild Type p53 Protein in Human Astrocytomas¹

Molecular Neuro-Oncology Laboratory, Neurosurgical Service [M-P. R., D. N. L.], Department of Pathology (Neuropathology) [D. N. L.], and Molecular Neurogenetics Laboratory, Neurology Service [J. F. G.], Massachusetts General Hospital and Harvard Medical School, Howe Laboratory of Ophthalmology, Massachusetts Eye and Ear Infirmary and Harvard Medical School [D. W. Y.], Boston, Massachusetts 02114; Institute for Neuropathology, University of Bonn, Bonn, Germany [A. V. D., O. D. W.]

We have previously described 10 astrocytomas with accumulation of p53 protein but no mutations in p53 exons 5–8, and we have suggested that they might represent overexpression of wild type protein or mutations in less conserved regions of the gene. To investigate these possibilities further, we studied the tumors with immunohistochemistry for wild type and mutant p53 protein and showed that all cases stained with the wild type PAb 1801 antibody but only one case stained with the mutant-specific PAb 240 antibody. To support the hypothesis that the accumulated p53 protein is wild type in most cases, we used single-strand conformation polymorphism analysis and DNA sequencing to evaluate p53 exons 4, 9, and 10 and did not detect mutations at these loci. Although the product of the MDM2 oncogene binds wild type p53 and may account for p53 accumulation, slot-blot analysis of these astrocytomas did not detect MDM2 gene amplification. Thus, evidence suggests that some astrocytomas may accumulate wild type p53 protein but not as a result of MDM2 gene amplification. Furthermore, PAb 1801 immunohistochemistry may not be an adequate method of screening astrocytomas for p53 mutations.

¹ Supported by American Cancer Society Grant CB-31A (D. N. L.) and NIH Grant CA 57683 (J. F. G., D. N. L.).

² To whom requests for reprints should be addressed, at Molecular Neuro-Oncology Laboratory, CNY6, Massachusetts General Hospital, Charlestown, MA 02129.

Received 4/29/93. Accepted 6/17/93.

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