Yoshida K, Sugino T, Tahara H, Woodman A, Bolodeoku J, Nargund V, Fellows G, Goodison S, Tahara E, Tarin D
Nuffield Department of Pathology, University of Oxford, John Radcliffe Hospital, United Kingdom.
Cancer. 1997 Jan 15;79(2):362-9. doi: 10.1002/(sici)1097-0142(19970115)79:2<362::aid-cncr20>3.0.co;2-y.
Telomerase is an enzyme that can reconstitute the ends (telomeres) of chromosomes after cell division and thus circumvent the cumulative damage that occurs in normal adult somatic cells during successive mitotic cycles. Recently, it has been proposed that this enzyme should, therefore, be detectable in immortal malignant cells but not in their normal counterparts, which stop dividing and senesce. Accordingly, telomerase activity has been reported in many types of malignant tumors, including those of the gastrointestinal tract, breast, and lung but little information was available regarding its status in bladder carcinoma or in exfoliated cancer cells.
In the current study, telomerase activity was examined by a polymerase chain reaction-based assay designated TRAP (telomeric repeat amplification protocol) in tissue samples from 56 bladder carcinomas, 17 nonneoplastic bladder lesions, and 2 dysplastic lesions of the urinary tract. The feasibility of identifying cancer patients by the detection of telomerase activity in exfoliated cancer cells in the urine was also investigated. Such activity was assayed in centrifuged urine cell pellets from 26 bladder carcinoma patients and from 83 patients with no evidence of malignant disease.
Evidence of telomerase was detected in solid tissue specimens from 48 of the 56 bladder carcinomas (86%) regardless of tumor stage or differentiation, whereas it was not found in any normal bladder tissue specimen. However, it was present in the dysplastic bladder lesions as well as in nearly all Stage I well differentiated carcinomas, suggesting that its activation occurs for the early stages of carcinogenesis and could perhaps be a useful marker for the detection of early primary or recurrent bladder tumors. Telomerase activity was detected with various signal intensities in urine specimens from 16 of the 26 patients with bladder carcinoma (62% sensitivity), whereas only 3 of 83 nonmalignant urine samples showed any activity (96.4% specificity); this was very weak.
These results suggest that telomerase could be a good diagnostic marker for the early noninvasive identification of patients with bladder carcinoma by facilitating the detection of exfoliated immortal cancer cells in their urine.
端粒酶是一种在细胞分裂后能够重建染色体末端（端粒）的酶，从而避免正常成人体细胞在连续有丝分裂周期中发生的累积性损伤。最近，有人提出，因此这种酶应该在永生化的恶性细胞中可检测到，而在其正常对应细胞中则检测不到，正常对应细胞会停止分裂并衰老。相应地，已经报道在许多类型的恶性肿瘤中存在端粒酶活性，包括胃肠道、乳腺和肺部的肿瘤，但关于其在膀胱癌或脱落癌细胞中的状态的信息很少。
在本研究中，通过一种基于聚合酶链反应的检测方法（端粒重复序列扩增法，TRAP）检测了56例膀胱癌组织样本、17例非肿瘤性膀胱病变组织样本和2例尿路发育异常病变组织样本中的端粒酶活性。还研究了通过检测尿液中脱落癌细胞的端粒酶活性来识别癌症患者的可行性。对26例膀胱癌患者和83例无恶性疾病证据患者的离心尿细胞沉淀进行了这种活性检测。
在56例膀胱癌中的48例（86%）实体组织标本中检测到端粒酶证据，无论肿瘤分期或分化程度如何，而在任何正常膀胱组织标本中均未发现。然而，它存在于发育异常的膀胱病变以及几乎所有I期高分化癌中，这表明其激活发生在致癌作用的早期阶段，可能是检测早期原发性或复发性膀胱肿瘤的有用标志物。在26例膀胱癌患者的16例尿液标本中检测到不同信号强度的端粒酶活性（敏感性62%），而83例非恶性尿液样本中只有3例显示有任何活性（特异性96.4%）；这种活性非常弱。
这些结果表明，端粒酶可能是通过促进检测尿液中脱落的永生化癌细胞来早期无创识别膀胱癌患者的良好诊断标志物。
