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Open Access Highly Accessed Research article

Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC)

Motoyuki Hashiguchi1, Shinichi Ueno12*, Masahiko Sakoda1, Satoshi Iino1, Kiyokazu Hiwatashi1, Koji Minami1, Kei Ando1, Yuko Mataki1, Kosei Maemura1, Hiroyuki Shinchi1, Sumiya Ishigami1 and Shoji Natsugoe1

Author Affiliations

1 Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan

2 Department of Clinical Oncology, Course of Advanced Therapeutics, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan

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BMC Cancer 2013, 13:572  doi:10.1186/1471-2407-13-572

Published: 5 December 2013

Abstract

Background

While recent research has shown that expression of ZEB-1 in a variety of tumors has a crucial impact on patient survival, there is little information regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study investigated the co-expression of ZEB-1 and E-cadherin in HCC by immunohistochemistry and evaluated its association with clinical factors, including patient prognosis.

Methods

A total of 108 patients with primary HCC treated by curative hepatectomy were enrolled. ZEB-1 expression was immunohistochemically categorized as positive if at least 1% cancer cells exhibited nuclear staining. E-cadherin expression was divided into preserved and reduced expression groups and correlations between ZEB-1 and E-cadherin expression and clinical factors were then evaluated.

Results

With respect to ZEB-1 expression, 23 patients were classified into the positive group and 85 into the negative group. Reduced E-cadherin expression was seen in 44 patients and preserved expression in the remaining 64 patients. ZEB-1 positivity was significantly associated with reduced expression of E-cadherin (p = 0.027). Moreover, significant associations were found between ZEB-1 expression and venous invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p = 0.025). Reduced E-cadherin expression was significantly associated with intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients with both ZEB-1 positivity and reduced E-cadherin expression had a poorer prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a significant prognostic factor by multivariate analysis. There was no statistical difference in overall survival when E-cadherin expression was reduced in the ZEB-1 positive group (p = 0.24).

Conclusions

Positive ZEB-1 expression and loss of E-cadherin expression are correlated with poor prognosis in HCC patients and malignancy of ZEB-1 positive tumors involves EMT.

Keywords:
Hepatocellular carcinoma; Hepatic resection; ZEB-1; E-cadherin; EMT