title: Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.
abstract: BACKGROUND
  Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs.
  
  
  METHODS
  We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry.
  
  
  RESULTS
  A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018).
  
  
  CONCLUSIONS
  We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment.
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Sideras
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: Bots
authors.affiliation: Erasmus University Medical Center, Department of Pathology, Be-231, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Biermann
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Sprengers
authors.affiliation: Erasmus University Medical Center, Department of Surgery, H-822k, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: W G
authors.initials: WG
authors.lastname: Polak
authors.affiliation: Erasmus University Medical Center, Department of Surgery, H-822k, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: J N M
authors.initials: JN
authors.lastname: IJzermans
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: R A
authors.initials: RA
authors.lastname: de Man
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Q
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Erasmus University Medical Center, Erasmus MC Cancer Institute, Department of Oncology, He-116 's Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Sleijfer
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bruno
authors.affiliation: Erasmus University Medical Center, Department of Gastroenterology and Hepatology, NA-1009, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kwekkeboom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D019353:Endemic Diseases; D005060:Europe / Q000453:epidemiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005843:Geography; D006509:Hepatitis B / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm