Detection of human telomerase reverse transcriptase (hTERT) expression in tissue and pancreatic juice from pancreatic cancer
Detection of human telomerase reverse transcriptase (hTERT) expression in tissue and pancreatic juice from pancreatic cancer
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DOI：
10.1016/j.surg.2007.07.042
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发表时间：
2008-01-01
期刊：
影响因子：
3.8
通讯作者：
Hiyama, Eiso
中科院分区：
文献类型：
--
作者：
Hashimoto, Yasushi;Murakami, Yoshiaki;Hiyama, Eiso
背景人端粒酶逆转录酶（Human telomerase reverse transcriptase，hTERT）是端粒酶的催化亚单位，是胰腺癌的一种有希望的诊断候选酶。为评价免疫组化（IHC）诊断胰腺癌的可行性，检测了胰腺组织、离体刷检和各种胰腺疾病的胰液标本中hTERT表达和端粒酶活性。采用TRAP法检测85例胰腺肿瘤标本、17例离体胰管刷检标本和27例胰液标本的端粒酶活性，采用免疫组化法检测hTERT。在组织样本中，当特异性设定为100%时，端粒酶活性在83%的浸润性导管腺癌（IDC）中呈阳性，而hTERT在88%的IDC中高表达。在导管内乳头状黏液性肿瘤（IPMNs），端粒酶活性水平逐渐增加，而hTERT的表达可检测到8个恶性IPMNs和2个交界性IPMNs的1。结果：11例IDC中10例hTERT阳性，4例恶性IPMN中3例hTERT阳性，其中7例细胞学检查未确诊为恶性，hTERT免疫组化诊断胰腺癌的敏感性为87%，特异性为92%，总准确率为89%，而细胞学检查的敏感性为53%。联合检测hTERT表达和端粒酶活性可提高敏感性达100%。我们的研究结果表明，hTERT在上皮细胞中的表达预示着胰腺肿瘤的恶性转化，免疫组化检测来自胰液的细胞中的hTERT为癌症诊断提供了一种有效的方法。
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.