Aim: This work aims to evaluate H3K27me3 expression in luminal-like breast tumors, using immunohistochemistry assay, to assess the prognostic value of this epigenetic alterations in estrogen positive breast cancer (BrC).
Introduction: BrC is the second most incident cancer worldwide. In Portugal, in 2012, BrC was simultaneously the leading cancer in incidence and mortality in women.1 Around 70% of all BrC are hormone-receptor positive, that is the major part of breast tumors is luminal-like.2 H3K27m3 is a gene repression marker3,4 and is associated with gene silencing, playing a crucial role in cell proliferation and differentiation.3 H3K27me3 may have some clinical value in several types of cancer since it can be used as a biomarker. This histone modification has been associated with poor prognosis of some BrC subtypes.5
Methods: It was used a cohort of BrC patients of the Portuguese Oncology Institution of Porto (IPO-Porto), diagnosed between 1994 and 2002. A total of 102 luminal-like tumor cases were assessed by immunohistochemistry, to H3K27me3 expression. To verify the prognostic value of H3K27me3 levels, Cox regression with a log rank test was performed for both disease-specific and disease-free survival.
Results: Through the result analysis, it was established that only tumor grade (p=0.021) was significant associated with disease-specific survival. Nevertheless, both luminal subtype (p=0.016) and H3K27me3 expression (p=0.012) were significantly associated with disease-free survival. Indeed, H3K27me3 high expression is associated with higher recurrence risk, especially in Luminal A.
Conclusion: We could confirm the prognostic value of H3K27me3 expression in luminal A subtype BrC patients. Therefore, higher H3K27me3 expression in luminal A tumors is associated with a greater probability of recurrence.
However, studies in larger cohorts are mandatory to validate its clinical utility.
Acknowledgements: This study was funded by a grant of the Research Centre of Portuguese Oncology Institute of Porto (CI-IPOP-74-2016).
References
- 1.Ferlay JSI, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, et al. 2013. GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11, International Agency for Research on Cancer, Lyon, France. [Google Scholar]
- 2.Senkus E, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rutgers E, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl. 5), v8-30 [DOI] [PubMed] [Google Scholar]
- 3.Chase A, Cross NC. Aberrations of EZH2 in cancer. Clin Cancer Res. 2011;17:2613-2618. [DOI] [PubMed] [Google Scholar]
- 4.Yoo KH, Hennighausen L. EZH2 methyltransferase and H3K27 methylation in breast cancer. Int J Biol Sci. 2012;8:59-65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Hayashi A, Yamauchi N, Shibahara J, Kimura H, Morikawa T, Ishikawa S, et al. Concurrent activation of acetylation and tri-methylation of H3K27 in a subset of hepatocellular carcinoma with aggressive behavior. PLoS ONE. 2014;9:e91330. [DOI] [PMC free article] [PubMed] [Google Scholar]
