EZH2 protein: a promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

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Gut doi:10.1136/gut.2010.231993

Paper

Hepatology

EZH2 protein: a promising immunomarker for the detection of hepatocellular

carcinomas in liver needle biopsies

Mu-Yan Cai1,2,

Zhu-Ting Tong1,

Fang Zheng1,

Yi-Ji Liao1,

Yi Wang1,

Hui-Lan Rao1,2,

Yang-Chao Chen3,

Qiu-Liang Wu1,2,

Yan-Hui Liu4,

Xin-Yuan Guan1,

Marie C Lin1,3,

Yi-Xin Zeng1,

Hsiang-Fu Kung1,3,

Dan Xie1

+ Author Affiliations

1State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen

University, Guangzhou, China

2Department of Pathology, Cancer Center, Sun Yat-Sen University, Guangzhou,

China

3State Key Laboratory of Oncology in South China, Chinese University of Hong

Kong, Hong Kong, China

4Department of Pathology and Laboratory Medicine, Guangdong Provincial People's

Hospital, Guangzhou, Guangdong, China

Correspondence to Dr Dan Xie, State key Laboratory of Oncology in South China,

Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, 510060

Guangzhou, China; xied@...

Contributors MYC, ZTT and FZ contributed equally to this study. Each author who

contributed to this work has been listed as an author on the paper.

Revised 19 January 2011

Accepted 20 January 2011

Published Online First 17 February 2011

Abstract

Background and aims 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.

Conclusion 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.