title: Angiopoietin-2 serum levels are elevated in patients with liver cirrhosis and hepatocellular carcinoma.
abstract: OBJECTIVE
  Liver cirrhosis is characterized by remodeling leading to nodules that are difficult to discern from hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) serum levels are used for the screening for HCC, with limited success. We evaluated angiopoietin-2 as a serum marker in patients with cirrhosis and with HCC.
  
  
  METHODS
  In a retrospective study, we measured angiopoietin-2 serum levels in 131 patients with HCC, 180 patients with cirrhosis, and 40 healthy controls. We also determined AFP serum levels in patients with HCC and compared the test characteristics of both serum markers. The expression patterns of angiopoietin-2 were determined by in situ hybridization in healthy and cirrhotic livers as well as in HCC.
  
  
  RESULTS
  Angiopoietin-2 serum levels were elevated in patients with liver cirrhosis (P < 0.0001) compared with healthy controls. Levels were further elevated in patients with HCC compared with healthy controls (P < 0.0001) and cirrhotic patients (P < 0.0001). The combination with AFP measurements led to improved discrimination between HCC and cirrhosis. Angiopoietin-2 message was present in tumor cells of HCCs but was absent from hepatocytes of cirrhotic and healthy livers. In cirrhosis, message was detected within the strands of fibrous tissue.
  
  
  CONCLUSIONS
  Serum angiopoietin-2 levels are elevated in patients with cirrhosis, implicating a possible role of the angiopoietin-Tie-2 system for neoangiogenesis in cirrhosis. Serum levels are further elevated in patients with HCC, suggesting the potential use of angiopoietin-2 as a marker for the detection of cirrhosis and HCC.
authors.affiliation: Department of Hepatology and Gastroenterology, CVK, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Scholz
authors.forename: Vanessa Annina
authors.initials: VA
authors.lastname: Rehm
authors.forename: Svenja
authors.initials: S
authors.lastname: Rieke
authors.forename: Katja
authors.initials: K
authors.lastname: Derkow
authors.forename: Petra
authors.initials: P
authors.lastname: Schulz
authors.forename: Konrad
authors.initials: K
authors.lastname: Neumann
authors.forename: Inga
authors.initials: I
authors.lastname: Koch
authors.forename: Maria
authors.initials: M
authors.lastname: Pascu
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008103:Liver Cirrhosis / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood; D012372:ROC Curve; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D042702:Angiopoietin-2; D014408:Biomarkers, Tumor