胰腺癌组织及胰液中人类端粒酶逆转录酶（hTERT）表达的检测

Detection of human telomerase reverse transcriptase (hTERT) expression in tissue and pancreatic juice from pancreatic cancer.

作者信息

Hashimoto Yasushi, Murakami Yoshiaki, Uemura Kenichiro, Hayashidani Yasuo, Sudo Takeshi, Ohge Hiroki, Fukuda Emi, Sueda Taijiro, Hiyama Eiso

机构信息

Department of Surgery, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.

出版信息

Surgery. 2008 Jan;143(1):113-25. doi: 10.1016/j.surg.2007.07.042.

DOI:10.1016/j.surg.2007.07.042

PMID:18154939

Abstract

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.

摘要

背景

人端粒酶逆转录酶（hTERT）是端粒酶的催化亚基，是一种很有前景的胰腺癌诊断候选指标。为评估免疫组织化学（IHC）诊断胰腺癌的可行性，我们检测了患有各种胰腺疾病的胰腺组织、离体刷检样本及胰液样本中的hTERT表达和端粒酶活性。

方法

采用端粒重复序列扩增法（TRAP）分析85例胰腺肿瘤样本、17例离体胰管刷检样本及27例胰液样本中的端粒酶活性，并用免疫组织化学法检测hTERT。

结果

在组织样本中，当特异性设定为100%时，83%的浸润性导管腺癌（IDC）中端粒酶活性呈阳性，而88%的IDC中hTERT高表达。在导管内乳头状黏液性肿瘤（IPMN）中，端粒酶活性水平在进展过程中逐渐升高，而8例恶性IPMN中的8例及2例交界性IPMN中的1例可检测到hTERT表达。在胰液样本中，11例IDC中的10例及4例恶性IPMN中的3例表达hTERT，其中7份样本在细胞学检查中未被诊断为恶性。基于hTERT免疫组织化学诊断胰腺癌的敏感性为87%，特异性为92%，总体准确率为89%，而细胞学检查的敏感性为53%。hTERT表达和端粒酶活性的额外评估可将敏感性提高至100%。