Immunohistochemical detection of acetylation and phosphorylation of histone H3 in brain tumors

M Horky, MD,a M Smrcka, MD, PhDb

aInstitute of Pathophysiology Masaryk University Brno Medical School, South Moravia Czech Republic, b Neurosurgical Department, Masaryk University Brno Medical School, University Hospital Brno, Brno, South Moravia, Czech Republic

Aim: Histones bind in a sequence-independent manner to form chromatin. The amini-terminal tails of histones are targets for both phosphorylation and acetylation events. These modifications are thought to fundamentally regulate chromatin structure to accommodate transcription, DNA replication, mitosis and DNA repair. The aim of the study was to detect phosphorylated and acetylated forms of H3 (histone-3) in brain tumors: meningioma, astrocytoma and glioblastoma multiforme. Methods: Paraffin-embedded sections from patients whose ages ranged from 36 to 72 yrs, undergoing routine histopathological verification were selected. The sections were evaluated according to the traditional nomenclature. The specimens comprised 5 meningioma, 5 astrocytoma, 4 glioblastoma multiforme. The sections were stained with polyclonal antibodies against phosphorylated and acetylated forms of H3. Results: We found nuclear positivity for phosphorylated (P) and acetylated (A) forms of H3 in all cases of glioblastoma multiforme (26%P, 43%A) and astrocytoma (15%P,23 %). The meningioma sections were negative for both markers. Conclusion: We revealed a marked association of histone H3 modifications with the progression of malignancy of brain tumors. Our results are in agreement with recent findings: (1) staining of cells with anti-phospho-histone H3 antibodies provides a highly specific marker for mitosis.(2) acetylation of nucleosomal histones correlates with localized transcriptional activity.

KEY WORDS: histones, mitosis, brain tumor.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.