trypsinogen and Bile-Duct-Neoplasms

Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-alpha(1)-antitrypsin for cholangiocarcinoma and to compare them with CA19-9 and CEA.. The study consisted of 84 patients with either PSC or cholangiocarcinoma or both referred for liver transplantation or other liver surgery. The serum concentrations were determined by time-resolved immunofluorometric assays.. Forty-six patients were transplanted due to PSC; in 3 of the explanted livers cholangiocarcinoma was found incidentally. All transplanted patients had severe biliary strictures together with cirrhosis or pre-cirrhosis. Twenty-nine of 38 patients with cholangiocarcinoma were candidates for intervention. In all, 8 patients had both PSC and cholangiocarcinoma. Receiver-operating characteristics curve analysis showed that serum trypsinogen-2 had the highest accuracy in differentiating between cholangiocarcinoma and PSC. The area under the curve (AUC) value was 0.804 for trypsinogen-2 and 0.613 for CA19-9. Serum trypsinogen-2 also showed the highest accuracy for differentiation between PSC and PSC with simultaneous cholangiocarcinoma with an AUC value of 0.759.. Our results suggest that serum trypsinogen-2 is a most useful marker for diagnosing patients with cholangiocarcinoma, and it is superior to serum CA19-9 and CEA.

Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; CA-19-9 Antigen; Cholangiocarcinoma; Constriction, Pathologic; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Receptors, Cell Surface; Sensitivity and Specificity; Trypsin; Trypsinogen

Serum concentrations of trypsinogen-2 and trypsin-2-alpha(1)-antitrypsin (trypsin-2-AAT) were determined in 145 patients with malignant and 61 with benign digestive-tract diseases. The validity of these tests for detection of cancer was compared with that of CA 19-9 and CEA. Elevated levels of trypsinogen-2 (>90 micrograms/l) and trypsin-2-AAT (>25 micrograms/l) were found in 46% and 42%, respectively, of patients with malignant disease and the levels of trypsinogen-2 were significantly higher than in those with benign disease (p<0.005). High trypsinogen-2 and trypsin-2-AAT concentrations were found most often in patients with biliary and pancreatic cancer, but also in benign obstructive biliary disease. Our results suggest that trypsinogen-2 and trypsin-2-AAT are new potential markers for cholangiocarcinomas.

Topics: alpha 1-Antitrypsin; Amylases; Bile Duct Neoplasms; Bilirubin; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular; Cholangiocarcinoma; Digestive System Diseases; Digestive System Neoplasms; False Positive Reactions; Humans; Liver Neoplasms; Pancreatic Neoplasms; Trypsin; Trypsinogen

We evaluated in situ expression of pancreatic trypsinogen (PT) and cathepsin B (CB) in 10 normal livers, 37 cholangiocarcinomas (CCs), and 36 hepatocellular carcinomas (HCCs). In normal livers, PT was expressed in intrahepatic large bile ducts, septal bile ducts, and peribiliary glands, and CB was present in hepatocytes and all epithelial cells of the intrahepatic biliary system. In CCs, PT was present in 26 (70%), of which 24 expressed PT both in CC cells and the CC stroma, and the remaining two showed PT only in CC cells. The ratio of PT-positive cases was high in well-differentiated CCs, moderate in moderately differentiated CCs, and low in poorly differentiated CCs. PT in the CC stroma was present in continuity with PT-positive CC cells, suggesting that PT was secreted from CC cells. The CC stroma positive for PT frequently showed destructive features. CB was present in 32 CCs (86%) and located in both CC cells and the CC stroma. All PT-positive CCs simultaneously expressed CB, suggesting a close association of PT and CB. In HCCs, in contrast, PT was not present in any cases. CB was present in 33 HCCs (92%) and located in both HCC cells and the HCC stroma. In positive specimens, PT immunoreactivity was finely granular in the cytoplasm, whereas CB immunoreactivity was diffuse in the entire cytoplasm. These data suggest that after malignant transformation CCs and HCCs continue to express PT and CB, and CB, respectively. It seems possible that PT secreted from CC cells is converted into trypsin by CB, and that trypsin and CB play a role in CC invasion by degrading extracellular matrix proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Hepatocellular; Cathepsin B; Cholangiocarcinoma; Female; Humans; Liver; Liver Neoplasms; Male; Middle Aged; Pancreas; Trypsin; Trypsinogen