Kavaler E, Landman J, Chang Y, Droller M J, Liu B C
Department of Urology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Cancer. 1998 Feb 15;82(4):708-14. doi: 10.1002/(sici)1097-0142(19980215)82:4<708::aid-cncr14>3.0.co;2-1.
In an attempt to find a more sensitive and specific noninvasive assay for the detection of bladder carcinoma, the authors assayed exfoliated cells from patients' voided urine for the presence of telomerase, an enzyme that maintains a cell's chromosomal length and is thought to be active in the transformation of normal somatic cells into immortal human tumor cells.
The authors used a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay to determine the presence of telomerase activity in voided urine samples from patients with known but yet untreated bladder carcinoma (n = 104) and from patients with hematuria of benign causes (n = 47). For 88 of the patients with bladder carcinoma, cytology was determined independently of the telomerase results or the pathology findings.
Of the 104 bladder carcinoma specimens, 88 (85%) tested positive for the presence of telomerase. Seventy-nine percent (23 of 29) of the Grade 1 tumors, 84% (32 of 38) of the Grade 2 tumors, and 87.5% (28 of 32) of the Grade 3 tumors were positive for telomerase activity. Five patients with carcinoma in situ (100%) were also positive. Telomerase activity was not found in 31 of 47 patients with bladder calculi, benign urethral stricture, benign prostatic hyperplasia, or inflammation. In the 16 patients (34%) who did have a false-positive result when tested for telomerase, all had either chronic or severe inflammation, including 1 patient with an inverted papilloma, 1 patient with cystitis cystica, and 1 patient with cystitis glandularis. However, for 35 normal, healthy volunteers whose voided urine samples were also assayed for the presence of telomerase activity, none was found. By comparison, only 51% (45 of 88) of the cytology samples from patients with bladder carcinoma yielded positive findings, whereas 49% (43 of 88) resulted in false-negative readings for tumors. Only 13% (3 of 23) of the Grade 1 tumors, 44% (14 of 32) of the Grade 2 tumors, and 82% (23 of 28) of the Grade 3 tumors were diagnosed by cytology. All five patients with carcinoma in situ were positive for cytology as well as for telomerase activity. When cytology was compared with the PCR-based telomerase assay in determining the presence of bladder carcinoma, the difference in the overall detection rates (85% for telomerase vs. 51% for cytology) was significant (P < 0.001). Furthermore, when telomerase activity was compared with cytology for low grade lesions (Grades 1 and 2), the difference in the detection rates (82% for telomerase vs. 31% for cytology) was also significant (P < 0.001).
Urinary cytology yields poor results for low grade tumors. This study shows the possible application of the telomerase assay in detecting bladder carcinoma, in particular low grade tumors, in voided urine samples.
为了找到一种更敏感、更特异的非侵入性检测膀胱癌的方法，作者检测了患者晨尿中脱落细胞中端粒酶的存在情况。端粒酶是一种维持细胞染色体长度的酶，被认为在正常体细胞转化为永生的人类肿瘤细胞过程中发挥作用。
作者采用基于聚合酶链反应（PCR）的端粒重复序列扩增法（TRAP），检测已知患有但尚未治疗的膀胱癌患者（n = 104）和良性血尿患者（n = 47）晨尿样本中端粒酶活性的存在情况。对于88例膀胱癌患者，细胞学检查独立于端粒酶检测结果或病理检查结果进行。
104份膀胱癌标本中，88份（85%）端粒酶检测呈阳性。1级肿瘤中79%（29例中的23例）、2级肿瘤中84%（38例中的32例）、3级肿瘤中87.5%（32例中的28例）端粒酶活性呈阳性。5例原位癌患者（100%）也呈阳性。47例膀胱结石、良性尿道狭窄、良性前列腺增生或炎症患者中，31例未检测到端粒酶活性。在16例（34%）端粒酶检测出现假阳性结果的患者中，均患有慢性或严重炎症，包括1例内翻性乳头状瘤患者、1例囊性膀胱炎患者和1例腺性膀胱炎患者。然而，对35名正常健康志愿者的晨尿样本进行端粒酶活性检测，均未发现阳性结果。相比之下，膀胱癌患者的细胞学样本中只有51%（88例中的45例）呈阳性结果，而49%（88例中的43例）对肿瘤检测结果为假阴性。1级肿瘤中只有13%（23例中的3例）、2级肿瘤中44%（32例中的14例）、3级肿瘤中82%（28例中的23例）通过细胞学检查确诊。所有5例原位癌患者细胞学检查和端粒酶活性检测均呈阳性。在确定膀胱癌的存在时，将细胞学检查与基于PCR的端粒酶检测进行比较，总体检测率存在显著差异（端粒酶检测为85%，细胞学检测为51%，P < 0.001）。此外，对于低级别病变（1级和2级），将端粒酶活性与细胞学检查进行比较时，检测率也存在显著差异（端粒酶检测为82%，细胞学检测为31%，P < 0.（此处原文有误，应为P < 0.001）
尿细胞学检查对低级别的肿瘤效果不佳。本研究表明端粒酶检测在检测晨尿样本中的膀胱癌，尤其是低级别肿瘤方面具有潜在应用价值。
