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

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.

Targeting the Nuclear Receptor-Binding SET Domain Family of Histone Lysine Methyltransferases for Cancer Therapy: Recent Progress and Perspectives

“…NSD1 is associated with several cancers, including acute myeloid leukemia and lung cancer. , In comparison, NSD2 is associated with a broad spectrum of malignancies due to gene translocation, overexpression, and mutation . Moreover, several reports have suggested that NSD2 is overexpressed in various cancers including multiple myeloma, skin, lung, bladder, prostate, and brain cancers. ,− Furthermore, Nakayama et al also identified NSD2 as a potential target in metaplastic breast cancer. NSD3 promotes cell-cycle progression and proliferation by activating signaling pathways and plays essential roles in the development of breast and small-cell lung cancers and pancreatic adenocarcinoma. , In addition, Kang et al reported that the knockdown of NSD3 expression suppressed proliferation of liver, bladder, and lung cancer cell lines by inducing G 2 /M cell cycle arrest.…”

EZH2 Expression in Follicular Lymphoma Is Variable and Independent from the Progression of Disease Within 24 Months of First Treatment

“…Conversely, in neoplastic cells, it activates transcription and stimulates proliferation. EZH2 alterations, both protein overexpression and mutations, were described in both solid tumors, i.e., breast (14)(15)(16)(17)(18), hepatocellular (19,20), gastric (21), urothelial (22,23), prostate carcinomas (24,25), melanoma (26,27) and in non-Hodgkin's lymphomas (NHL) i.e., diffuse large B-cell lymphoma (DLBCL), FL, Burkitt lymphoma and other small cell and aggressive B-cell NHL (28,29). The inferior impact of EZH2 overexpression on overall survival has been outlined independently (30).…”