Angiopoietin-2 serum levels are elevated in patients with liver cirrhosis and hepatocellular carcinoma.
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.
Scholz
Arne
A
Department of Hepatology and Gastroenterology, CVK, Charité Universitätsmedizin Berlin, Berlin, Germany.
Rehm
Vanessa Annina
VA
Rieke
Svenja
S
Derkow
Katja
K
Schulz
Petra
P
Neumann
Konrad
K
Koch
Inga
I
Pascu
Maria
M
Wiedenmann
Bertram
B
Berg
Thomas
T
Schott
Eckart
E
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
D042702:Angiopoietin-2; D014408:Biomarkers, Tumor