title: Prognostic significance of aminopeptidase-N (CD13) in hepatoblastoma.
abstract: BACKGROUND
  Hepatoblastoma is a rare childhood malignant tumor that originates from immature hepatic cells. Aminopeptidase-N(CD13), an ectopeptidase that promotes tumor invasion and metastasis, is expressed in fetal stage hepatic progenitor cells, although its role in hepatoblastoma remains unclear.
  
  
  METHODS
  The expression pattern of CD13 was investigated on immunohistochemistry in 30 tissue samples from 27 hepatoblastoma patients (16 with predominantly embryonal [pE] histology and 14 with predominantly fetal [pF] histology). Immunoreactive score (IRS) was used to quantify staining data, and the relationship between CD13 expression, clinicopathological factors, and clinical outcome was investigated. The biological function of CD13 was also examined in the hepatoblastoma cell lines Huh6 and HepG2.
  
  
  RESULTS
  All specimens stained positive for CD13, with higher CD13 expression in pE than in pF hepatoblastoma samples (median IRS, 4; range, 2-9 vs 2; range, 1-4). Strong CD13 expression was correlated with vascular invasion. Five year event-free survival and overall survival were better in patients with CD13(low) than in those with CD13(high) tumors (100% vs 51.0%, P = 0.026; and 100% vs 74.0%, P = 0.114, respectively). A CD13-neutralizing antibody and the potent CD13 inhibitor, Ubenimex, suppressed invasive activity in HepG2 cells in vitro.
  
  
  CONCLUSIONS
  CD13 expression is associated with hepatoblastoma invasiveness and could be a novel prognostic marker for hepatoblastoma.
authors: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Satoshi
authors: S
authors: Saida
authors: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Ken-ichiro
authors: K
authors: Watanabe
authors: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Itaru
authors: I
authors: Kato
authors: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Hisanori
authors: H
authors: Fujino
authors: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Katsutsugu
authors: K
authors: Umeda
authors: Division of Hepato-pancreato-biliary Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Shinya
authors: S
authors: Okamoto
authors: Division of Hepato-pancreato-biliary Surgery and Transplantation, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Shinji
authors: S
authors: Uemoto
authors: Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Tomoro
authors: T
authors: Hishiki
authors: Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Hideo
authors: H
authors: Yoshida
authors: Division of Clinical Trial Design and Management, Translational Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Shiro
authors: S
authors: Tanaka
authors: Department of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Souichi
authors: S
authors: Adachi
authors: Department of Clinical Applications, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors: Akira
authors: A
authors: Niwa
authors: Department of Clinical Applications, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
authors: Tatsutoshi
authors: T
authors: Nakahata
authors: Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Toshio
authors: T
authors: Heike
mesh_terms: D001706:Biopsy; D018826:CD13 Antigens / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018197:Hepatoblastoma / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology / Q000473:pathology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D018826:CD13 Antigens
keywords: aminopeptidase-N/CD13; hepatoblastoma; invasion; liver tumor; pediatric oncology