EZH2 and MMSET Were Identified as Potentially Useful Therapeutic Targets in Metaplastic Breast Carcinoma

Anticancer Res. 2020 Apr;40(4):2133-2139. doi: 10.21873/anticanres.14172.

Abstract

Background/aim: Metaplastic breast carcinoma (MBC) is a rare malignancy, which is often triple-negative for the hormone receptors and human epidermal growth factor receptor 2, and thus, does not benefit from targeted therapy. In this study, we examined the expression of methylation and demethylation enzymes by immunostaining MBC and the adjacent normal tissues or triple-negative ductal carcinoma (TNDC), and identified alterations that may be used as therapeutic targets.

Materials and methods: We retrospectively studied surgical specimens from 15 patients who underwent surgery for MBC at Kanagawa Cancer Center between 2005 and 2016, and similarly from 14 patients with TNDC. The frequencies of high methylation/demethylation enzyme expression were compared among them.

Results: The frequencies of high enhancer of zeste homolog 2 (EZH2) and multiple myeloma SET domain (MMSET) expression were significantly higher in both MBC and TNDC than in normal tissue.

Conclusion: EZH2 and MMSET may be useful therapeutic targets in MBC.

Keywords: EZH2; MMSET; Metaplastic breast carcinoma; epigenetics.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Female
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Metaplasia / diagnosis
  • Metaplasia / genetics*
  • Metaplasia / pathology
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / genetics
  • Repressor Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Repressor Proteins
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • NSD2 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2