Activation of telomerase and its diagnostic application in biopsy specimens from biliary tract neoplasms.

Abstract

Telomerase activity has been reported to have potential as a useful diagnostic marker for cancer in various organs. The authors previously reported that telomerase activity in pancreatic juice differentiates pancreatic ductal carcinoma from adenoma and pancreatitis. In the current study, the usefulness of semiquantitatively determined telomerase activity in the diagnosis of malignant biliary tract neoplasms was investigated. The samples examined included 61 surgically resected biliary tract tissues (11 gallbladder carcinomas, 5 bile duct carcinomas, 1 gallbladder adenoma, 30 cholecytitis cases, 7 cholesterol polyps, 1 normal gallbladder, and 6 normal common bile duct tissues), 42 bile samples from patients with biliary tract or pancreatic disease (19 cases of malignant biliary tract disease, 11 cases of benign biliary tract disease, 10 cases of malignant pancreatic disease, and 2 cases of benign pancreatic disease), and 14 bile duct biopsy specimens collected by percutaneous transhepatic choledochoscopy or endoscopic retrograde cholangiopancreatography (8 bile duct carcinoma specimens, 1 bile duct adenoma specimen, and 5 hepatolithiasis specimens). In biliary tract tissues, a telomerase ladder was detected in 73% of gallbladder carcinomas, 40% of bile duct carcinomas, and none of the other biliary tract tissues. One gallbladder adenoma showed a weak telomerase ladder. The telomerase ladder was detected in the bile sample from 1 patient (5.3%) with malignant biliary tract disease, none of the patients with benign biliary tract disease, 5 patients (50%) with malignant pancreatic disease, and none of the patients with benign pancreatic disease. In biopsy specimens, the telomerase ladder was detected in 75% of patients with bile duct carcinoma but not in any of the patients with hepatolithiasis. The median value of relative telomerase activity in the patients with bile duct carcinoma was significantly higher than that in the patients with hepatolithiasis. The diagnosis of bile duct carcinoma was confirmed preoperatively by histopathologic examination in only 25% of the biopsy specimens. The results of the current study indicate that telomerase is highly activated in biliary tract carcinomas and that the detection of a telomerase ladder in biopsy samples is an excellent tool for the diagnosis of bile duct carcinomas.