title: EZH2 protein: a promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies.
abstract: OBJECTIVE
  A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC.
  
  
  METHODS
  Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort.
  
  
  RESULTS
  Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs.
  
  
  CONCLUSIONS
  Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.
authors.affiliation: State key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.forename: Zhu-Ting
authors.initials: ZT
authors.lastname: Tong
authors.forename: Fang
authors.initials: F
authors.lastname: Zheng
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Liao
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Rao
authors.forename: Yang-Chao
authors.initials: YC
authors.lastname: Chen
authors.forename: Qiu-Liang
authors.initials: QL
authors.lastname: Wu
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
authors.forename: Marie C
authors.initials: MC
authors.lastname: Lin
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: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D004812:Epidemiologic Methods; D005260:Female; D053673:Glypicans / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C105937:GPC3 protein, human; D053673:Glypicans; D018840:HSP70 Heat-Shock Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2