title: Impact of stem cell marker expression on recurrence of TACE-treated hepatocellular carcinoma post liver transplantation.
abstract: BACKGROUND
  Liver transplantation is the most effective therapy for cirrhosis-associated hepatocellular carcinoma (HCC) but its utility is limited by post-transplant tumor recurrence. Use of the Milan, size-based criteria, has reduced recurrence rate to less than 10% but many patients remain ineligible. Reduction of tumor size with local therapies has been used to "downstage" patients to allow them to qualify for transplantation, but the optimal criteria to predict tumor recurrence in these latter patients has not been established. The existence of a progenitor cell population, sometimes called cancer stem cells (CSCs), has been proposed to be one mechanism accounting for the chemotherapy resistance and recurrence of hepatocellular carcinoma. The aim of this study was to determine if transcatheter arterial chemoemolization (TACE) treated tumors have increased CSC marker expression and whether these markers could be used to predict tumor recurrence.
  
  
  METHODS
  Formalin fixed specimens were obtained from 39 HCC liver explants (23 with no treatment and 16 after TACE). Immunohistochemical staining was performed for EpCAM, CD44, CD90, and CD133. Staining for each marker was scored 0-3 by evaluating the number and intensity of positive tumor cells in 5 hpf of tumor in each specimen.
  
  
  RESULTS
  TACE treated tumors displayed greater necrosis and fibrosis than non-TACE treated samples but there were no differences in morphology between the viable tumor cells of both groups. In TACE treated specimens, the staining of both EpCAM and CD133 was greater than in non-TACE specimens but CD44 and CD90 were the same. In the TACE group, the presence of high EpCAM staining was associated with tumor recurrence. Four of ten EpCAM high patients recurred while 0 of 6 EpCAM low patients recurred (P = 0.040). None of the other markers predicted recurrence.
  
  
  CONCLUSIONS
  High pre-transplant EpCAM staining predicted HCC recurrence. This suggests that the abundance of tumor cells with a CSC phenotype may be a critical factor in the likelihood of tumor recurrence in patients receiving liver transplantation after TACE.
authors.affiliation: Beijing 302th Hospital, Beijing 100039, People’s Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zeng
authors.forename: Jinyu
authors.initials: J
authors.lastname: Ren
authors.forename: Maura
authors.initials: M
authors.lastname: O'Neil
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Brian
authors.initials: B
authors.lastname: Bridges
authors.forename: Josiah
authors.initials: J
authors.lastname: Cox
authors.forename: Bashar
authors.initials: B
authors.lastname: Abdulkarim
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Schmitt
authors.forename: Sean C
authors.initials: SC
authors.lastname: Kumer
authors.forename: Steven A
authors.initials: SA
authors.lastname: Weinman
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000096:biosynthesis; D016461:Chemoembolization, Therapeutic; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule