A Case of Gallbladder Carcinoma Diagnosed Preoperatively by the Detection of Human Telomerase Reverse Transcriptase mRNA in Endoscopically Obtained Gallbladder Bile

It is difficult to accurately diagnose the nature of polypoid lesions in the gallbladder. To increase diagnostic accuracy, we have developed an endoscopic technique for obtaining gallbladder bile, termed endoscopic transpapillary catheterization into the gallbladder (ETCG). We describe here a case of gallbladder carcinoma diagnosed preoperatively by the detection of human telomerase reverse transcriptase (hTERT) mRNA, a catalytic subunit of telomerase, in gallbladder bile obtained using the ETCG technique. A patient with a polypoid lesion 15 mm in diameter in the gallbladder was admitted to our hospital for further examinations. Gallbladder bile collected by the ETCG technique was evaluated cytologically and also analyzed for telomerase activity and hTERT mRNA. Although the results for cytology and telomerase activity were negative, that for hTERT mRNA was positive. Open surgery was carried out and it was confirmed that the lesion was an adenocarcinoma invading the subserosa. The molecular biological analysis of gallbladder bile collected using the ETCG technique was shown to be effective for diagnosing the nature of the polypoid lesion in the gallbladder.

References

• 1 Harley C B, Futcher A B, Greider C W. Telomeres shorten during aging of human fibroblast.  Nature. 1990;  345 458-460
• 2 Shay J W, Bacchetti S. A survey of telomerase activity in human cancer.  Eur J Cancer. 1997;  33 787-791
• 3 Hiyama E, Kodama T, Shinbara K. et al . Telomerase activity is detected in pancreatic cancer but not in benign tumors.  Cancer Res. 1997;  57 326-331
• 4 Morales C P, Burdick J S, Saboorian M H. et al . In situ hybridization for telomerase RNA in routine cytologic brushings for the diagnosis of pancreaticobiliary malignancies.  Gastrointest Endosc. 1998;  48 402-405
• 5 Hirabayashi S, Nakatsu T, Nishioka M. The double contrast method by endoscopic transpapillary catheterization in the gallbladder.  Dig Endosc. 1990;  2 40-46
• 6 Wada E, Hisatomi H, Moritoyo T. et al . Genetic diagnostic test of hepatocellular carcinoma by telomerase catalytic subunit mRNA.  Oncol Rep. 1998;  5 1407-1412
• 7 Yahata N, Nagao K, Ohyashiki J. et al . Improvement in detecting telomerase activity using silica-based resin treatment: an experience of urine in bladder carcinoma.  Int J Oncol. 1999;  14 709-712
• 8 Hisatomi H, Nagao K, Kanamaru T. et al . Levels of telomerase catalytic subunit mRNA as a predictor of potential malignancy.  Int J Oncol. 1999;  14 727-732
• 9 Almoguera C, Shibata D, Forrester K. et al . Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.  Cell. 1988;  53 549-559
• 10 Berthelemy P, Bouisson M, Escourrou J. et al . Identification of K-ras mutations in pancreatic juice in the early diagnosis of pancreatic cancer.  Ann Intern Med. 1995;  123 188-191
• 11 Tada M, Omata M, Kawai S. et al . Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma.  Cancer Res. 1993;  53 2472-2474
• 12 Watanabe H, Yamaguchi Y, Ha A. et al . Quantitative determination of K-ras mutations in pancreatic juice for diagnosis of pancreatic cancer using hybridization protection assay.  Pancreas. 1998;  17 341-347
• 13 Itoi T, Shinohara Y, Takeda K. et al . Detection of telomerase activity in biopsy specimens for diagnosis of biliary tract cancers.  Gastrointest Endosc. 2000;  52 380-386
• 14 Niiyama H, Mizumoto K, Kusumoto M. et al . Activation of telomerase and its diagnostic application in biopsy specimens from biliary tract neoplasms.  Cancer. 2000;  85 2138-2143
• 15 Feng J, Funk W D, Wng S S. et al . The RNA component of human telomerase.  Science. 1995;  269 1236-1241
• 16 Harrington L, McPhail T, Mar V. et al . A mammalian telomerase-associated protein.  Science. 1997;  275 973-977
• 17 Nakamura T N, Morin G B, Champman K B. et al . Telomerase catalytic subunit homologues from fission yeast and human.  Science. 1997;  277 955-959
• 18 Itoi T, Shinohara Y, Takeda K. et al . Detection of telomerase reverse transcriptase mRNA in biopsy specimens and bile for diagnosis of biliary tract cancers.  Int J Mol Med. 2001;  7 281-287
• 19 Takakura M, Kyo S, Kanaya T. et al . Expression of human telomerase subunits and correlation with telomerase activity in cervical cancer.  Cancer Res. 1998;  58 1558-1561
• 20 Glabrenner B, Ardan M, Boeck W. et al . Prospective evaluation of brush cytology of biliary strictures during endoscopic retrograde cholangiopancreatography.  Endoscopy. 1999;  31 712-717