Expression of H3K4me3 and H3K9ac in breast cancer

Aim Breast cancer is the leading cause of cancer death in females. Histone modifications have been shown to have an influence on the gene expression. This study focusses on the histone modifications H3K9ac and H3K4me3 in breast cancer and their impact on survival.

Material and Methods H3K4-trimethylated (H3K4me3) and acetylated H3 (H3K9ac) expression was immunohistochemically examined in 235 tissue samples.

Results Positive estrogen receptor status was correlated to a higher IRS of the nuclear (p = 0.033), and of the cytoplasmic H3K4me3 staining (p = 0.009). H3K9ac intensity was associated with positive Her2-status (p = 0.045) and with poor prognosis in cells with positive (more than 14 % of cancer cells) Ki67-status (p = 0.013). A high intensity of nuclear H3K4me3 staining was found to be correlated to a lower 10-year-survival (p = 0.026) and to a lower breast cancer-specific-survival (p = 0.004). High percentage-Score (>190) of H3K9ac expression was correlated to worse breast cancer-specific-survival (p = 0.005). Shorter progression-free survival was found in patients with nuclear (p = 0.013) and cytoplasmic H3K4me3expression (p = 0.024) and H3K9ac expression (p = 0.023).

Conclusion This analysis provides new evidence of histone modifications in breast cancer. High H3K4me3 and H3K9ac expression was correlated to survival rates. Further investigation of histone modifications in breast cancer could lead to a more profound understanding of the molecular mechanisms of cancer development and could result in new therapeutic strategies.

Funding Internal departmental funding.

 

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Interessenkonflikt

Thomas Kolben has a relative employed at Roche and holds stock of Roche. Theresa M. Kolben is employed at Roche and holds stock of Roche. Sven Mahner has received Research support, advisory board, honoraria and travel expenses from AstraZeneca, Clovis, Eisai, GlaxoSmithKline, Medac, MSD, Novartis, Olympus, PharmaMar, Roche, Sensor Kinesis, Teva, Tesaro. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. All other authors declare that they have no conflict of interest.

Publication History

Article published online:
07 October 2020