Overexpression of enhance of Zeste homolog 2 (EZH2) in endometrial carcinoma: An NRG Oncology/Gynecologic Oncology Group Study

Abstract

Objectives-Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that mediates epigenetic silencing of tumor suppressor genes. It is commonly over-expressed in several solid tumors and has been shown to be a prognostic biomarker. We investigated patterns of EZH2 expression in endometrial cancer. Methods-Evaluation of EZH2 expression was completed on both early and advanced stage endometrioid adenocarcinoma tissues and a subset of matched normal mullerian tissue samples, from participants enrolled in Gynecologic Oncology Group (GOG) protocol 210, using real time reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB) analysis. Nonparametric methods were used to assess differences in mRNA and protein expression respectively with known clinical/pathologic prognostic factors. Survival analysis was performed using techniques including Cox proportional hazards (PH) model to evaluate differences in progression free survival (PFS) and overall survival (OS) based on EZH2 expression. Results-Eighty-seven patient samples were analyzed that included 60 tumors and 27 matchednormal tissue specimens. EZH2 mRNA (p < .0001) and protein expression (p < .0001) in tumor specimens were significantly higher than in matched-normal tissue. In primary tumors, EZH2 protein expression was associated with lympho-vascular space invasion (LVSI, p = .044), and EZH2 mRNA expression was associated with age (p = .037). Differences in EZH2 expression between primary tumors and matched normal tissue were not associated with other known clinical and pathologic factors. However, there did appear to be a trend toward decreased progression-free survival among patients with high EZH2 expression levels. Conclusions-Our results confirm the differential expression of EZH2 in uterine cancers compared to normal tissues. However, there were no statistically significant differences in survival associated with EZH2 expression in patients with endometrial cancer.

EZH2: a novel target for cancer treatment

“…EZH2 overexpression was first identified in prostate cancer and associated with poor clinical outcomes [ 22 ]. More researches show evidences of EZH2 overexpression in many other cancer types, including breast cancer [ 23 ], esophageal cancer [ 24 ], gastric cancer [ 25 ], anaplastic thyroid carcinoma [ 26 ], nasopharyngeal carcinoma [ 27 ], and endometrial carcinoma [ 28 ]. IHC assessment of 62 samples shows that EZH2 expression is significantly higher in BAP1-mutant renal clear cell carcinoma patients with progressed stage, grade, nodal invasion, and metastasis [ 29 ].…”

Establishment of a novel cell cycle-related prognostic signature predicting prognosis in patients with endometrial cancer

“…Interestingly, EZH2 has been shown to be an oncogene and promote EnCa progression by multiple studies, which is consistent with our findings [ 33 – 35 ]. For example, EZH2 mRNA and protein expression in EnCa specimens were significantly higher than in matched-normal tissue [ 36 ]. Besides, EZH2 siRNA in combination with taxanes produced more robust anti-tumor effects versus those induced by monotherapies [ 37 ].…”

Targeting Epigenetic Regulators for Endometrial Cancer Therapy: Its Molecular Biology and Potential Clinical Applications

“…The expression level of H3K27me3 did not differ between EC and normal endometrium [ 86 ]. However, Krilla et al [ 87 ] and Oki et al [ 88 ] observed that EZH2, which is responsible for H3K27me3, was overexpressed in EC compared to that in normal endometrium and is associated with poor prognosis. Dysregulation of H3K27me3 by EZH2 was found in various types of cancers [ 86 , 87 ].…”