title: Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC).
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.
authors.affiliation: Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medicine and Dental Sciences, Kagoshima, Japan. ueno1@m.kufm.kagoshima-u.ac.jp.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Hashiguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sakoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iino
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Hiwatashi
authors.forename: Koji
authors.initials: K
authors.lastname: Minami
authors.forename: Kei
authors.initials: K
authors.lastname: Ando
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mataki
authors.forename: Kosei
authors.initials: K
authors.lastname: Maemura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shinchi
authors.forename: Sumiya
authors.initials: S
authors.lastname: Ishigami
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
mesh_terms: D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1