P53 MUTATION AND PROTEIN ALTERATION IN 50 GLIOMAS - RETROSPECTIVE STUDY BY DNA-SEQUENCING TECHNIQUES AND IMMUNOHISTOCHEMISTRY

Alterations of the p53 protein, which is a 53 kD phosphoprotein and ge ne product of the p53 gene, has been found to play a major role in the genesis of a variety of human malignancies including tumors of the ce ntral nervous system. We investigated 50 tumor specimens from primary central nervous system neoplasms. Tissue samples were screened for mut ations by the single-strand conformation polymorphism method and detec ted mutations were sequenced. All tissue specimens were stained immuno histochemically for p53 protein, which when altered accumulates in the nucleus due to prolonged half-life. Mutations were found in six cases , including one pilocytic astrocytoma World Health Organisation anapla stic astrocytomas WHO grade III, and one primitive neuroectodermal tum or (PNET). In terms of relative frequency mutations were found mostly in the group of anaplastic astrocytomas WHO grade III. Interestingly, no mutations were found in the group of investigated glioblastomas. p5 3 immunopositivity did not correlate with the mutations found, whereas the staining index was significantly higher in the cases with detecte d mutations than in those without. When p53 alteration is seen as an i ndicator for different pathogenic pathways in glioma formation, this s tudy gives evidence for a difference between anaplastic astrocytoma an d glioblastoma. However, since there was a great overlap in p53 immuno positivity and p53 mutation in tumors of different WHO grades and enti ties, it seems that p53 will not act as a marker molecule neither for tumor entities nor for tumor malignancy.