Abstract
Abstract Objectives: Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase 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 in breast, renal, and gastric cancers. This study aims to investigate patterns of EZH2 expression in endometrial cancer. Methods: Evaluation of expression of EZH2 was completed on both early and advanced stage endometrioid adenocarcinoma tissues and a subset of matched normal mullerian tissue samples, from participants enrolled in GOG protocol 210, using real time reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB) analysis. Investigators were blinded to clinical data. One-way ANOVA, F test and Fisher's exact test were used to assess differences in log mRNA and protein expression respectively with known clinical and pathologic prognostic factors. Kaplan Meier survival analysis was used to evaluate differences in progression free survival (PFS) based on EZH2 expression. Results: Eight-seven specimens were analyzed including 60 tumors and 27 normal tissue specimens. EZH2 mRNA and protein expression in tumor specimens was significantly higher than in matched controls (paired t test, p < 0.001). EZH2 expression was associated with lympho-vascular space invasion (p = 0.044) but other clinical and pathologic factors including age, stage, grade, nodal involvement or disease status were not associated with significant differences in expression. However, there does appear to be a trend towards decreased progression free survival among patients with increased EZH2 expression levels. Conclusions: Our results confirm that there is differential expression of EZH2 in uterine cancers compared to normal tissues and suggests a potential role of the EZH2 as prognostic marker of aggressive disease in patients with endometrial cancer. In view of the substantial portion of early stage low grade tumors expressing EZH2, it will be interesting to investigate if increased EZH2 protein levels may also have therapeutic implications, since targeted inhibition of EZH2 expression has been shown to repress tumor cell growth in other solid malignancies. Further investigation into this potential prognostic biomarker and therapeutic target is warranted. Citation Format: Lauren Krill, Shamshad Ali, Ramez Eskander, Meenakshi Singh, David Mutch, Susan Zweizig, Michael Birrer, Heather Lankes, Bang Hoang, Leslie Randall. Overexpression of enhancer of zeste homolog 2 (EZH2) in endometrial carcinoma: evidence from an NRG Oncology/Gynecologic Oncology Group trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4752.
Published Version
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