title: Cancer stem cell marker expression alone and in combination with microvascular invasion predicts poor prognosis in patients undergoing transplantation for hepatocellular carcinoma.
abstract: BACKGROUND
  The cancer stem cell hypothesis provides an explanation for hepatocellular carcinoma (HCC) heterogeneity. We investigated the expression of CD44 and CD133 alone and in combination with microvascular invasion (MVI) as predictors of prognosis in patients undergoing liver transplantation for HCC.
  
  
  METHODS
  Explanted livers from 95 patients transplanted for HCC were analyzed. Marker expression was evaluated by immunofluorescence.
  
  
  RESULTS
  Seventy-seven patients were male with a mean age of 56 years. The most common etiologies of cirrhosis were hepatitis C (50%) and alcoholic liver disease (41%). Forty-one patients had laboratory model for end-stage liver disease score greater than 15. Overall survival (OS) at 1-, 3-, and 5-years was 86%, 75%, and 64%, respectively. Recurrence rate was 13% with a median follow-up of 64 months. The 5-year OS was significantly lower in those patients with MVI and CD44 (36.9%) or CD133 (40%). CD44(+) and CD133(+) correlated with increased risk of poorly differentiated HCC, and elevated alpha-fetoprotein levels. In combination with MVI, both markers were independently associated with increased recurrence and worse OS (recurrence P < .003, odds ratio = 8.05; P = .001, odds ratio = 9.5, survival P = .001, HR = 3.7; P = .004, HR = 3.2 respectively).
  
  
  CONCLUSIONS
  CD44 or CD133 alone and in combination with MVI are independent predictors of poor prognosis in patients undergoing transplantation for HCC.
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA; Department of Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors.forename: Valery
authors.initials: V
authors.lastname: Vilchez
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Lilia
authors.initials: L
authors.lastname: Turcios
authors.affiliation: Markey Cancer Center - University of Kentucky, Lexington, KY, USA.
authors.forename: Yekaterina
authors.initials: Y
authors.lastname: Zaytseva
authors.affiliation: Markey Cancer Center - University of Kentucky, Lexington, KY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Stewart
authors.affiliation: Department of Pathology, University of Kentucky, Lexington, KY, USA.
authors.forename: Eun Y
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Maynard
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Malay B
authors.initials: MB
authors.lastname: Shah
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Daily
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Ching-Wei D
authors.initials: CW
authors.lastname: Tzeng
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Davenport
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA.
authors.forename: Ana Lia
authors.initials: AL
authors.lastname: Castellanos
authors.affiliation: Department of Radiology, University of Kentucky, Lexington, KY, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Krohmer
authors.affiliation: Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hosein
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA; Markey Cancer Center - University of Kentucky, Lexington, KY, USA.
authors.forename: Bernard Mark
authors.initials: BM
authors.lastname: Evers
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, KY, USA. Electronic address: rgeda2@uky.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Gedaly
mesh_terms: D000071916:AC133 Antigen / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis / Q000096:biosynthesis; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D055806:Microvessels / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D000509:alpha-Fetoproteins
keywords: Hepatocellular carcinoma; Liver cancer stem cells; Liver transplantation; Outcomes; Prognostic factors