AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling.

METHODS: Oligonucleotide arrays (Affymetrix U133A) were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding non-malignant liver tissue. To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed.

RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 probes significantly up-regulated, 331 probes down-regulated; P < 0.05; fold change > 2; ≥ 70%) were identified. Using these data and two-dimensional cluster analysis, a specific gene expression profile was obtained allowing fast and reproducible differentiation of CCC, which was confirmed by supervised neuronal network modelling. The most consistently overexpressed gene (median fold change 33.5, significantly overexpressed in 100%) encoded osteopontin. Furthermore, an association of various genes with the histopathological grading could be demonstrated.

CONCLUSION: A highly specific gene expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against non-malignant liver tissue and other liver masses. The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin. These data may lead to a better understanding of human cholangiocarcinogenesis.

• Cholangiocarcinoma
• Oligonucleotide arrays
• Osteopontin
• Cell cycle regulation
• Gene expression

AIM: The diagnosis of cholangiocarcinoma is often difficult, making management approaches problematic. A reliable serum marker for cholangiocarcinoma would be a useful diagnostic test. The aims of our study were to evaluate the usefulness of a serum CA19-9 determination in the diagnosis of cholangiocarcinoma.

METHODS: We prospectively measured serum CA19-9 and CEA concentrations in patients with cholangiocarcinoma (n = 35), benign biliary diseases (n = 92), and healthy individuals (n = 15). Serum CA19-9 and CEA concentrations were measured by an immunoradiometric assay without knowledge of the clinical diagnosis.

RESULTS: The sensitivity of a CA19-9 value > 37 KU·L^-1 and a CEA value > 22 μg·L^-1 in diagnosing cholangiocarcinoma were 77.14% and 68.57%, respectively. When compared with the benign biliary diseases group, the true negative rates of serum CA19-9 and CEA were 84.78% and 81.52%, respectively. The false positive rates of serum CA19-9 and CEA were 15.22% and 18.48%, whereas the accuracy of serum CA19-9 and CEA were 82.68% and 77.95%, respectively. Serum CA19-9 and CEA concentrations were significantly elevated (P < 0.001 and P < 0.05) in patients with cholangiocarcinoma (290.31 ± 5.34 KU·L^-1 and 36.46 ± 18.03 μg·L^-1) compared with patients with benign biliary diseases (13.38 ± 2.59 KU·L^-1 and 13.84 ± 3.85 μg·L^-1) and healthy individuals (12.78 ± 3.69 KU·L^-1 and 11.48 ± 3.37 μg·L^-1). In 15 patients undergoing curative resection of cholangiocarcinoma, the mean serum CA19-9 concentration was decreased from a preoperative level of 286.41 ± 4.36 KU·L^-1 to a postoperative level of 62.01 ± 17.43 KU·L^-1 (P < 0.001), and the mean serum CEA concentration from 39.41 ± 24.35 μg·L^-1 to 28.69 ± 11.03 μg·L^-1(P < 0.05). In patients with cholangiocarcinoma, however, no correlation was found between serum CEA and CA19-9 concentrations (r = 0.036).

CONCLUSION: These data suggest that the serum CA19-9 determination is a useful addition to the available tests for the differential diagnosis of cholangiocarcinoma. Serum CA19-9 is an effective tumor marker in diagnosing cholangiocarcinoma, deciding whether the tumor has been radically resected and monitoring effect of treatment.

• Bile Duct Neoplasms/blood
• Bile Duct Neoplasms/diagnosis
• Bile Ducts, Intrahepatic
• CA-19-9 Antigen/blood
• Carcinoembryonic Antigen/blood
• Cholangiocarcinoma/blood
• Cholangiocarcinoma/diagnosis
• Humans