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2006 Abstracts: Diagnostic relevance of human telomerase reverse transcriptase (hTERT) expression detected by immunohistochemistry in pancreatic tumors
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Diagnostic relevance of human telomerase reverse transcriptase (hTERT) expression detected by immunohistochemistry in pancreatic tumors
Yasushi Hashimoto1, Eiso Hiyama2,1, Yoshiaki Murakami1, Kenichiro Uemura1, Yasuo Hayashidani1, Takeshi Sudo1, Yoichi Sugiyama1, Taijiro Sueda1; 1Department of Surgery, Graduate School of Biomedical Science, Hiroshima University, Hiroshima, Japan; 2Department of Biomedicine, Graduate School of Biomedical Science and Natural Science Center of Basic Research and Development, Hiroshima University, Hiroshima, Japan

Human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is considered as a useful diagnostic marker for cancers. But there were few studies to be attempted immunohistochemical detection of hTERT in pancreatic tumors. Objectives:To evaluate the feasibility of immunohistochemistry (IHC) of hTERT as diagnostic marker, we analyzed hTERT expression by IHC and compared with telomerase activity. Materials and Methods:Forty invasive ductal adenocarcinomas(IDCs), 69 intraductal papillary-mucinous neoplasms(IPMNs:31 adenomas, 10 borderline lesions, 14 non-invasive carcinomas, and 14 invasive carcinomas), 5 endocrine cell tumors, 5 mucinous cystic neoplasms, 5 solid pseudo-papillary tumors, 7 chronic pancreatitis, 5 normal pancreatic tissues, and 10 ex vivo brushing samples of the pancreatic duct were examined. These specimens were analyzed for hTERT expression by IHC and telomerase activity by TRAP assay. Results:There were significant correlations between hTERT expression and telomerase activity, indicating that accumulation of hTERT is a limiting step for the activity of telomerase. IHC could assess hTERT expression at the cellular level without complicated procedure than by TRAP assay. hTERT expression showed gradual stepwise increase with increasing degree of cellular atypia in IPMNs. One of 7 pancreatitis sample was positive for telomerase activity, derived from infiltrated lymphocytes, without detectable hTERT expression. In 10 ex vivo brushing samples, 5 of 5 with IDCs expressed hTERT with detectable telomerase activity, whereas 0 of 5 benign lesions did. In 4 IDCs and one adenoma of IPMN, hTERT was detected in some parts of tumor cells without detectable telomerase activity, however, these discordant results might be caused by the inherent heterogeneity of hTERT expression in these tumors. Conclusions:Immunohistochemical detection of the hTERT may be useful diagnostic value in carcinogenesis of pancreas and clinical applicability for preoperative diagnosis.
Positive rates of hTERT expression and telomerase activity in pancreatic tissues

Pancreatic diseases

n

hTERT expression

Telomerase activity

Invasive ductal carcinoma

40

87.5%

90.0%

IPMN adenoma

31

3.2%

10.0%

IPMN borderline lesion

10

10.0%

10.0%

IPMN non-invasive carcinoma

14

35.7%

75.0%

IPMN invasive carcinoma

14

85.7%

100.0%

Endocrine cell tumor

5

20.0%

20.0%

Mucinous cystic neoplasms

5

0%

0%

Solid pseudo-papillary tumor

5

0%

0%

Chronic pancreatitis

7

0%

14.3%

Normal pancreatic epithelium

5

0%

0%

ex vivo brushing sample

10

50.0%

50.0%


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