Myung Seung-Jae, Yang Suk-Kyun, Chang Hye-Sook, Byeon Jeong-Sik, Kim Kyu-Jong, Hong Seong Soo, Jeong Jin-Yong, Lee Sun-Mi, Hong Weon-Seon, Kim Jin-Ho, Min Young Il
Division of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
J Gastroenterol Hepatol. 2005 Oct;20(10):1578-83. doi: 10.1111/j.1440-1746.2005.03877.x.
Colorectal carcinoma (CRC) is a complication of ulcerative colitis (UC). Although stool occult blood and colonoscopy are used to detect CRC in UC, these methods have drawbacks, in that bleeding is associated with UC and the underlying mucosa is irregular, making it difficult to detect dysplasia. Telomerase and its catalytic subunit, telomerase reverse transcriptase (hTERT), are specifically expressed in cancers, making them candidate markers for the early detection of cancer. We previously reported that assays of telomerase in pancreatic juice may be useful for the early detection of pancreatic cancer. The aims of our study were to determine whether assays for telomerase and TERT may be useful in the diagnosis of CRC developed in UC patients.
Luminal washings and biopsies were collected during colonoscopy in 66 patients; 34 with CRC, 21 with UC, and 11 controls. Telomerase activity was detected by telomeric repeat amplification protocol (TRAP) and hTERT mRNA was assayed by reverse transcription-polymerase chain reaction (RT-PCR).
Telomerase activity was detected in biopsies from 33 of 34 (97%) CRC patients, 14 of 21 (67%) UC patients, and three of 11 (27%) normal controls. Expression of hTERT mRNA was observed in biopsies from 32 of 34 (94%) CRC patients, 12 of 21 (57%) UC patients, and five of 11 (45%) controls. In analyses of washing fluid, 21 of 34 (62%) of CRC patients were positive for telomerase, but all UC patients and controls were negative. The sensitivity of telomerase for CRC was 97% in tissues and 62% in washing fluid. The specificity of telomerase in washing fluid was 100%, whereas the specificity of telomerase or hTERT mRNA in tissues was 47% each.
For the detection of CRC arising in UC, telomerase and hTERT in colonic tissue showed high sensitivity, and telomerase in colonoscopic luminal washings revealed a high specificity. These might be candidate markers in clinical decision making for the diagnosis of CRC from UC.
结直肠癌(CRC)是溃疡性结肠炎(UC)的一种并发症。尽管粪便潜血检查和结肠镜检查用于检测UC患者的CRC,但这些方法存在缺陷,因为出血与UC相关且黏膜下层不规则,难以检测发育异常。端粒酶及其催化亚基端粒酶逆转录酶(hTERT)在癌症中特异性表达,使其成为癌症早期检测的候选标志物。我们之前报道过,检测胰液中端粒酶可能有助于胰腺癌的早期检测。本研究的目的是确定检测端粒酶和TERT是否有助于诊断UC患者发生的CRC。
在结肠镜检查期间收集66例患者的肠腔灌洗液和活检组织;其中34例患有CRC,21例患有UC,11例为对照。通过端粒重复序列扩增法(TRAP)检测端粒酶活性,通过逆转录聚合酶链反应(RT-PCR)检测hTERT mRNA。
在34例CRC患者中的33例(97%)、21例UC患者中的14例(67%)以及11例正常对照中的3例(27%)的活检组织中检测到端粒酶活性。在34例CRC患者中的32例(94%)、21例UC患者中的12例(57%)以及11例对照中的5例(45%)的活检组织中观察到hTERT mRNA表达。在对灌洗液的分析中,34例CRC患者中的21例(6)端粒酶呈阳性,但所有UC患者和对照均为阴性。端粒酶对CRC的敏感性在组织中为97%,在灌洗液中为62%。端粒酶在灌洗液中的特异性为100%,而端粒酶或hTERT mRNA在组织中的特异性均为47%。
对于检测UC患者发生的CRC,结肠组织中的端粒酶和hTERT显示出高敏感性,结肠镜检查肠腔灌洗液中的端粒酶显示出高特异性。这些可能是临床决策中诊断UC患者CRC的候选标志物。