Telomerase activity in periampullary tumors correlates with aggressive malignancy

Objective To determine the presence of telomerase activity in a variety of periampullary malignancies and pancreatic diseases and quantify its activit y to establish any association with the stage or aggressiveness of malignan cy. Summary Background Data Progressive shortening of telomeres, repetitive DNA sequences at the ends of chromosomes, plays a role in cell senescence. Tel omerase catalyzes conservation of telomeric repeats and may promote cell im mortality and hence malignancy. It is absent in normal tissues but upregula ted in more than 80% of cancers. Methods Fresh specimens of 62 periampullary tumors were snap-frozen in liqu id nitrogen and adjacent tissue was formalin-fixed for histopathology. The telomerase repeat amplification protocol (TRAP) was used to obtain telomera se DNA products. These were separated with gel electrophoresis, stained wit h SYBR green, and quantified by densitometry. Findings were confirmed with a fluorometric TRAP assay in which fluorescent primers specific for telomer ase were selectively amplified in its presence. Results Telomerase activity was upregulated in 26 of 33 periampullary malig nancies (79%): 17 of 21 pancreatic adenocarcinomas (81%), 2 of 2 cholangioc arcinomas, 2 of 2 duodenal carcinomas, and 5 of 8 ampullary carcinomas (63% ). Poorly differentiated periampullary tumors had significantly higher telo merase activity than well-differentiated tumors, and tumors larger than 2 c m had significantly higher telomerase activity than those 2 cm or smaller. Pancreatic ductal adenocarcinomas with lymph node metastases had significan tly greater activity than node-negative cancers. Two of 11 intraductal papi llary mucinous tumors were positive for telomerase activity, but only in fo ci of invasive carcinoma. Chronic pancreatitis (n = 7), serous cystadenomas (n = 5), benign mucinous cystic neoplasms (n = 4), neuroendocrine cancer ( n = 1), and acinar cell carcinoma (n = 1) had no detectable telomerase acti vity. Conclusion Telomerase activity is common in periampullary carcinomas. The m agnitude of activity correlates with aggressiveness in pancreatic adenocarc inoma and may prove useful as a molecular index for biologic staging.