trypsinogen and Carcinoma--Hepatocellular

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

To test the diagnostic utility of pancreatic digestive enzyme immunohistochemistry in liver cancers, the expression of three pancreatic digestive enzymes (trypsinogen, chymotrypsinogen and pancreatic lipase) was investigated in cholangiocarcinoma (CC) (n = 42), hepatocellular carcinoma (HCC) (n = 35), combined HCC-CC (n = 11) and metastatic adenocarcinoma (MA) of the liver (n = 34; 4 gastric cancer, 5 pancreatic cancer and 25 colon cancer). In CC, 15 (36%) expressed one or more of these enzymes, while the remaining 27 (64%) did not express any enzymes. In MA, 13 (38%) expressed one or more of these enzymes, while the remaining 21 (62%) did not express any enzymes. Expression of trypsinogen, chymotrypsinogen and lipase was noted in 15 CC (36%), 11 CC (25%) and 15 CC (36%), respectively, and in 9 MA (26%), 6 MA (18%) and 13 MA (38%), respectively. There was no significant difference in the positive ratio of each enzyme between CC and MA. In positive cases, the enzymes were expressed with a cytoplasmic granular pattern. In MA, there was no significant difference in the positive ratio of the enzymes among the primary sites. In contrast to CC and MA, these enzymes were not expressed in any cases of HCC and combined HCC-CC. These data suggest that pancreatic digestive enzyme immunohistochemistry may be useful for differential diagnosis between HCC and CC or MA as well as between combined HCC-CC and CC or MA, but it is not useful for differential diagnosis between CC and MA. A positive reaction for these enzymes is indicative of CC or MA and is against the diagnosis of HCC or combined HCC-CC, and a negative reaction is noncontributory to the differential diagnosis.

Topics: Adenocarcinoma; Aged; Carcinoma, Hepatocellular; Cholangiocarcinoma; Chymotrypsinogen; Colonic Neoplasms; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Liver Neoplasms; Male; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancrelipase; Stomach Neoplasms; 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