p53 mutation and protein alteration in 50 gliomas. Retrospective study by DNA-sequencing techniques and immunohistochemistry
K. von Eckardstein1, H. Gries1, E. Bolik1, J. Cervós-Navarro1, I.N. Tschairkin1 and S. Patt1,2
1Institute of Neuropathology, Free University of Berlin, Berlin and 21nstitute of Pathology, Friedrich-Schiller-University Jena, Jena, Germany
Offprint requests to: Prof. Stephan Pan, Institute of Pathology, FriedrichSchiller-University Jena, BachstraBe 18, 0-07740 Jena, Germany
Summary. Alterations of the p53 protein, which is a 53 kD phosphoprotein and gene 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 central nervous system. We investigated 50 tumor specimens from primary central nervous system neoplasms. Tissue samples were screened for mutations by the single-strand conformation polymorphism method and detected mutations were sequenced. All tissue specimens were stained immuno-' histochemically for p53 protein, which when altered accumulates in the nucleus due to prolonged halflife. Mutations were found in six cases, including one pilocytic astrocytoma World Health Organisation (WHO) grade I, two astrocytomas WHO grade II, two anaplastic astrocytomas WHO grade III, and one primitive neuroectodermal tumor (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. P53 immuDopositivity did not correlate with the mutations found, whereas the staining index was significantly higher in the cases with detected mutations than in those without. When p53 alteration is seen as an indicator for different pathogenic pathways in glioma formation, this study gives evidence for a difference between anaplastic astrocytoma and glioblastoma. However, since there was a great overlap in p53 immunopositivity and p53 mutation in tumors of different WHO grades and entities, it seems that p53 will not act as a marker molecule neither for tumor entities nor for tumor malignancy. Histol Histopathol 12, 611-616 (1997)
Key words: Glioma, p53, DNA sequencing, Immunohistochemistry, Diagnosis
DOI: 10.14670/HH-12.611