Melissourgos N, Kastrinakis N G, Davilas I, Foukas P, Farmakis A, Lykourinas M
Department of Urology, G. Gennimatas General Hospital, Athens, Greece.
Urology. 2003 Aug;62(2):362-7. doi: 10.1016/s0090-4295(03)00254-1.
To assess the value of the telomerase enzyme as a bladder cancer detection marker, we investigated the expression of the catalytic subunit of the complex (human telomerase reverse transcriptase [hTERT]) in the urine of patients with malignant or benign urinary lesions, as well as of healthy individuals, and compared the results with urine cytology.
Spontaneously voided samples were obtained from two groups of subjects: group 1, 146 previously untreated patients with a histologic diagnosis of transitional cell carcinoma or other urothelial neoplasm; and group 2, 128 control individuals, either healthy or with a nonmalignant bladder disease. Total RNA extracts from sedimented urothelial cells were analyzed by a reverse transcriptase-polymerase chain reaction assay for the presence of a 146-bp hTERT transcript. Urine samples were also examined by standard cytology.
Expression of hTERT was detected in 134 (92%) of 146 patients with bladder cancer, and only 64 (44%) yielded a positive result by cytology (P <0.001). The sensitivity advantage of the former technique became particularly evident in the detection of low-grade transitional cell carcinoma (93% versus 28%, P <0.001). Accordingly, the negative predictive value of the molecular assay was markedly greater than the one calculated for cytologic screening (91% versus 60%). On the other hand, both methods were at least 96% specific, with their positive predictive indexes exceeding 94%.
Our findings suggest that the assessment of hTERT expression in urine sediments represents a reliable tool for the detection of primary urothelial neoplasms, equally specific, yet far more sensitive, than conventional cytology.
为评估端粒酶作为膀胱癌检测标志物的价值，我们研究了恶性或良性泌尿系统病变患者以及健康个体尿液中该复合物催化亚基（人类端粒酶逆转录酶[hTERT]）的表达情况，并将结果与尿液细胞学检查结果进行比较。
从两组受试者中获取自然排尿样本：第1组为146例未经治疗且经组织学诊断为移行细胞癌或其他尿路上皮肿瘤的患者；第2组为128名对照个体，包括健康者或患有非恶性膀胱疾病者。通过逆转录聚合酶链反应分析沉淀的尿路上皮细胞中的总RNA提取物，以检测146 bp的hTERT转录本的存在情况。尿液样本也通过标准细胞学检查进行检测。
146例膀胱癌患者中有134例（92%）检测到hTERT表达，而细胞学检查仅有64例（44%）呈阳性结果（P<0.001）。前一种技术在检测低级别移行细胞癌方面的敏感性优势尤为明显（93%对28%，P<0.001）。因此，分子检测的阴性预测值明显高于细胞学筛查计算得出的阴性预测值（91%对60%）。另一方面，两种方法的特异性均至少为96%，其阳性预测指数均超过94%。
我们的研究结果表明，评估尿液沉淀物中hTERT的表达是检测原发性尿路上皮肿瘤的可靠工具，与传统细胞学检查一样具有特异性，但敏感性远高于传统细胞学检查。
