Open Access Open Badges Research

Enhancer of zeste homologue 2 (EZH2) is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors

Szofia Hajósi-Kalcakosz1, Katalin Dezső1, Edina Bugyik1, Csaba Bödör1, Sándor Paku14, Zoltán Pávai2, Judit Halász3, Krisztina Schlachter3, Zsuzsa Schaff3 and Péter Nagy1*

Author Affiliations

1 First Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllõi út 26, Budapest, H-1085, Hungary

2 Department of Anatomy and Embriology, University of Medicine and Pharmacy, Targu Mures, Romania

3 Second Department of Pathology, Semmelweis University, Budapest, Hungary

4 Tumor Progression Research Group, Joint Research Organization of the Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

For all author emails, please log on.

Diagnostic Pathology 2012, 7:86  doi:10.1186/1746-1596-7-86

Published: 18 July 2012



The immunohistochemical demonstration of Enhancer of zeste homologue 2 (EZH2) proved to be a useful marker in several tumor types. It has been described to distinguish reliably hepatocellular carcinomas from liver adenomas and other benign hepatocellular lesions. However, no other types of malignant liver tumors were studied so far.


To evaluate the diagnostic value of this protein in hepatic tumors we have investigated the presence of EZH2 by immunohistochemistry in hepatocellular carcinomas and other common hepatic tumors.

EZH2 expression was examined in 44 hepatocellular carcinomas, 23 cholangiocarcinomas, 31 hepatoblastomas, 16 other childhood tumor types (rhabdomyosarcoma, neuroblastoma, Wilms’ tumor and rhabdoid tumor), 17 metastatic liver tumors 24 hepatocellular adenomas, 15 high grade dysplastic nodules, 3 biliary cystadenomas, 3 biliary hamartomas and 3 Caroli’s diseases.


Most of the malignant liver tumors were positive for EZH2, but neither of the adenomas, cirrhotic/dysplastic nodules, reactive and hamartomatous biliary ductules stained positively.


Our immunostainings confirm that EZH2 is a sensitive marker of hepatocellular carcinoma, but its specificity is very low, since almost all the investigated malignant liver tumors were positive regardless of their histogenesis. Based on these results EZH2 is a sensitive marker of malignancy in hepatic tumors. In routine surgical pathology EZH2 could be most helpful to diagnose cholangiocarcinomas, because as far as we know this is the first marker to distinguish transformed and reactive biliary structures. Although hepatoblastomas also express EZH2, the diagnostic significance of this observation seems to be quite limited whereas, the structurally similar, other blastic childhood tumors are also positive.

Virtual Slides

The virtual slide(s) for this article can be found here:

Immunohistochemistry; EZH2; Hepatocellular carcinoma; Cholangiocarcinoma; Hepatoblastoma; Metastasis; Hepatocellular adenoma