title: High expression of EZH2 is associated with tumor aggressiveness and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.
abstract: The enhancer of zeste homolog 2 (EZH2), a known repressor of gene transcription, has been reported to be associated with biological malignancy in several cancers. The potential oncogenic role of EZH2 and its clinical/prognostic significance, however, in esophageal squamous cell carcinoma (ESCC) are unclear. In this study, the methods of immunohistochemistry and fluorescence in-situ hybridization were used to examine protein expression and amplification of EZH2 in 98 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (CRT). High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively. High EZH2 expression was significantly correlated with increased cell proliferation (p = 0.009), high histopathological grade (p = 0.002), regional (p = 0.025) and distant lymph node metastasis (p < 0.001) and lack of clinical complete response to CRT (p = 0.028). Univariate analysis revealed that high expression of EZH2 was associated with poor metastasis-free survival (MFS) (p = 0.003), poor progression-free survival (PFS) (p = 0.001) and poor disease-specific survival (DSS) (p < 0.001). In multivariate analysis, high expression of EZH2, together with lack of clinical complete response, were evaluated as significant independent prognostic factors of MFS, PFS and DSS for patients with ESCC. These findings suggest that high expression of EZH2 correlates with tumor aggressiveness and adverse patient outcome in ESCC treated with definitive CRT. Evaluation of EZH2 expressions might be useful for predicting tumor response to CRT and prognosis for patients with ESCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Li-Ru
authors.initials: LR
authors.lastname: He
authors.forename: Meng-Zhong
authors.initials: MZ
authors.lastname: Liu
authors.forename: Bin-Kui
authors.initials: BK
authors.lastname: Li
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.forename: Yang-Chao
authors.initials: YC
authors.lastname: Chen
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Hsiang-Fu
authors.initials: HF
authors.lastname: Kung
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D000071221:Enhancer of Zeste Homolog 2 Protein; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2