Immunohistochemical expression of histone modification pattern in adult glioblastoma

Abstract

Background: Despite the growing advances in molecular research and therapeutics, glioblastomas are still considered highly invasive aggressive tumors with a median survival of 15 months. Genetic alterations have been studied in detail; however, additionally, there is now growing evidence on the role of epigenetic alterations in glioblastoma. Recently, histone modification patterns have been found to have a significant part in gene expression and prognosis. However, further research in this field is warranted to establish its role for the betterment of these patients with the deadly disease.

Aims: To determine the immunohistochemical expression of histone modifications like histone-3-lysine-18 acetylation (H3K18Ac) and histone-4-lysine 20 trimethylation (H4K20triMe) in glioblastoma patients.

Materials and methods: This is a retrospective study of 48 glioblastoma patients who underwent surgery. Immunohistochemistry (IHC) for tri-methyl-histone-H4 (Lys20) (H4K20triMe) and acetyl-histone-H3 (Lys18) (H3K18Ac) was performed in paraffin-embedded tissues manually, and the expression was noted. Data on the mitotic index and overall survival was collected and statistically analyzed.

Results: The mean age was 50 years with a M: F ratio of 1.6:1. Out of 48 cases, 60% (28 cases) demonstrated positivity for H3K18Ac and 98% (46 cases) for H4K20triMe. The pattern of expression was nuclear with increased expression adjacent to necrosis and at the invasive front. The overall median Q score for H3K18Ac was 1/12 and for H4K20triMe was 6/12. No significant statistical significance was observed between histone expression, Ki67%, and overall survival.

Conclusion: Histone modification patterns are being explored in detail in an array of tumors. They also have a potential role in glioblastoma for risk stratification and instituting appropriate treatment based on the prognosis. Epigenetic changes like histone modification patterns, in addition to genetics, can pave the way for a better molecular understanding of glioblastomas and provide hope in the future to improve the survival of these patients with deadly diseases.