Angiopoietin-2 and biliary diseases: elevated serum, but not bile levels are associated with cholangiocarcinoma.
BACKGROUND
The diagnosis of cholangiocarcinoma (CC) is challenging especially in patients with primary sclerosing cholangitis (PSC) and often delayed due to the lack of reliable markers. Angiopoietin-2 (Angpt-2) has been employed as a biomarker of angiogenesis and might be involved in tumor neoangiogenesis.


OBJECTIVE
To evaluate the diagnostic potential of Angpt-2 as a biomarker to detect patients with CC.


METHODS
Bile and serum Angpt-2 levels were measured in patients with CC (n=45), PSC (n=74), CC complicating PSC (CC/PSC) (n=11) and patients with bile duct stones (n=37) in a cross sectional study. Diagnostic accuracy of Angpt-2 was compared to carbohydrate antigen 19-9 (CA19-9). Fluorescent immunohistochemistry from human CC liver tissue samples was performed to localize the origin of Angpt-2.


RESULTS
Serum Angpt-2 concentration was significantly elevated in patients with CC compared to control patients (p<0.05). Diagnostic accuracy of Angpt-2 as determined by receiver operating characteristic (ROC) analysis resulted in a higher area under the curve (AUC) value compared to CA19-9 (AUC: 0.85 versus 0.77; 95% confidence interval (CI): 0.74-0.93 versus 0.65-0.87, respectively). Angpt-2 was also detectable in bile, but was not associated with the presence of CC. Immunohistochemistry revealed a strong induction of Angpt-2 expression in the tumor vasculature.


CONCLUSIONS
Circulating Angpt-2 in serum might be a promising protein candidate locally derived from the tumor vasculature in patients with CC. Measurement of Angpt-2 in serum may be useful for diagnosis and further clinical management of patients with CC.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center - Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Torsten
T
Voigtländer
Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany.
Sascha
S
David
Department of Nephrology & Hypertension, Hannover Medical School, Hannover, Germany.
Kristina
K
Thamm
Institute of Pathology, Hannover Medical School, Hannover, Germany.
Jerome
J
Schlué
Mosaiques diagnostics GmbH, Hannover, Germany.
Jochen
J
Metzger
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center - Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Michael P
MP
Manns
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center - Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.
Tim O
TO
Lankisch
D042702:Angiopoietin-2 / Q000097:blood* / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood*; D018281:Cholangiocarcinoma / Q000097:blood* / Q000175:diagnosis*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005453:Fluorescence; D006801:Humans; D007150:Immunohistochemistry; D018709:Statistics, Nonparametric
D042702:Angiopoietin-2; D014408:Biomarkers, Tumor