Detection of human telomerase reverse transcriptase (hTERT) expression in tissue and pancreatic juice from pancreatic cancer.
BACKGROUND
Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is a promising diagnostic candidate for pancreatic cancer. To evaluate the feasibility of immunohistochemistry (IHC) for the diagnosis of pancreatic cancer, hTERT expression and telomerase activity were assayed in pancreatic tissues, ex vivo brushing, and pancreatic juice samples with various pancreatic diseases.


METHODS
Telomerase activity was analyzed using the TRAP assay and hTERT was examined by IHC in 85 pancreatic tumor samples, 17 ex vivo pancreatic duct brushings, and 27 pancreatic juice samples.


RESULTS
In tissue samples, telomerase activity was positive in 83% of invasive ductal adenocarcinomas (IDCs) when the specificity was set at 100%, while hTERT was highly expressed in 88% of IDCs. In intraductal papillary mucinous neoplasms (IPMNs), the levels of telomerase activity increased gradually during progression, while hTERT expression was detectable in 8 of 8 malignant IPMNs and 1 of 2 borderline IPMNs. In pancreatic juice samples, 10 of 11 IDCs and 3 of 4 malignant IPMNs expressed hTERT, in which seven samples were not diagnosed as malignant on cytologic exam. The diagnoses of pancreatic cancer based on hTERT IHC exhibited high rates of sensitivity (87%), specificity (92%), and overall accuracy (89%), whereas the sensitivity of cytologic examination was 53%. The additional assessment of hTERT expression and telomerase activity could improve the sensitivity up to 100%.


CONCLUSIONS
Our results suggested that hTERT expression in epithelia indicates malignant transformation in pancreatic tumors and immunohistochemical detection of hTERT in cells derived from pancreatic juice provides a potent method for cancer diagnosis.
D002288:Adenocarcinoma, Mucinous / Q000737:chemistry; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000737:chemistry / Q000473:pathology; D002291:Carcinoma, Papillary / Q000737:chemistry; D045744:Cell Line, Tumor; D002908:Chronic Disease; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010189:Pancreatic Juice / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000175:diagnosis* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis*
C509186:TERT protein, human; D019098:Telomerase