Increased EZH2 Expression is Associated With Proliferation and Progression of Cervical Cancer and Indicates a Poor Prognosis

Abstract

The objective of this study was to illustrate the role of enhancer zeste homolog 2 (EZH2) overexpression in the proliferation, progression, and prognosis of cervical cancer. We detected EZH2 and Ki-67 expression levels using immunohistochemical (IHC) studies in 20 normal cervical tissues, 50 cervical intraepithelial neoplasia (including 25 low-grade intraepithelial lesions and 25 high-grade intraepithelial lesions), and 101 cervical cancer tissues. The relationships between EZH2 expression and Ki-67 expression, conventional clinicopathologic characteristics of cervical cancer, and patient outcomes were evaluated. The effect of EZH2 expression on cancer-specific survival was assessed by multivariate Cox regression analysis. Positive expression of EZH2 was detected in 10% (2/20) of the normal cervical tissues, 52% (13/25) of the low-grade squamous intraepithelial lesions, 64% (16/25) of the high-grade squamous intraepithelial lesions, and 68.3% (69/101) of the cervical cancer tissues. The expression of Ki-67 was positively correlated with EZH2 expression: 5% (1/20) in normal cervical tissues, 48% (12/25) in low-grade squamous intraepithelial lesions, 52% (13/25) in high-grade squamous intraepithelial lesions, and 57.4% (58/101) in cervical cancer tissues. Overexpression of EZH2 was adversely associated with clinical stage, histologic differentiation, infiltration depth, and lymph node metastasis (P<0.05). Patients with EZH2-positive expression showed a decreased overall survival compared with those with EZH2-negative expression (P=0.003, log-rank test). Multivariate Cox regression analysis suggested that overexpression of EZH2 was an independent predictor of poor prognosis in cervical cancer. Overexpression of EZH2 was closely associated with the carcinogenesis, proliferation, clinical and biologic behaviors, and the prognosis of cervical cancer, suggesting that it might be used as a potential predictor of prognosis in cervical cancer.