Badawy Thoraya, El-Abd Shawki, Zahra Mohamed, Eid Manal, Abdou Said, El-Shazly Sherien
Department of Clinical Pathology, Tanta University, Tanta, Egypt.
Mol Med Rep. 2008 May-Jun;1(3):325-33.
This study was performed to evaluate the clinical utility of the measurement of the expression of telomerase enzyme (the catalytic subunit of the complex hTERT) and of the chromosomal analysis of urine by multicolor fluorescence in situ hybridization (M-FISH) assay for the detection of bladder cancer and its recurrence. These results were compared with those afforded by urine cytology, hematuria screening and the bladder tumor antigen (BTA) and fibrin degradation products (FDP) tests. Urine samples were obtained from three groups: 30 patients with bladder cancer, 15 patients with non-malignant bladder disorders and 8 healthy individuals. hTERT mRNA was measured by reverse transcription real-time PCR. M-FISH was performed using a mixture of fluorescent labeled probes for the centromeric regions of chromosomes 3, 7, 17, and the locus specific identifier p16 probe for the 9p21 locus. We demonstrated that the overall sensitivity of hemoglobin dipstick and the BTA and FDP tests was insignificantly greater than that of urine cytology, but with a lower specificity. The hTERT mRNA expression marker offered significantly greater sensitivity for detecting all bladder cancers, especially superficial and low grade tumors, than did urine cytology, and with a higher specificity. M-FISH was significantly more sensitive than urine cytology in detecting bladder tumors, but had lower specificity (insignificant results). The superior sensitivity of M-FISH was maintained when comparing the two assays in terms of low-stage and low grade tumor detection. M-FISH was the most sensitive and specific test in detecting tumor recurrence, followed by the BTA test. hTERT, hematuria screening and FDP showed relatively low sensitivity and low specificity during follow-up. Our findings suggest that the assessment of hTERT expression and chromosomal abnormalities in urine represent reliable tools - equally specific yet far more sensitive than conventional cytology - for the early detection of bladder cancer. The high sensitivity of FISH in detecting recurrence makes it useful for reducing the number of cyctoscopies usually performed in the accurate follow-up of these cases.
本研究旨在评估通过测量端粒酶（复合物hTERT的催化亚基）的表达以及采用多色荧光原位杂交（M-FISH）分析法对尿液进行染色体分析来检测膀胱癌及其复发的临床效用。将这些结果与尿液细胞学检查、血尿筛查以及膀胱肿瘤抗原（BTA）和纤维蛋白降解产物（FDP）检测所提供的结果进行比较。从三组人群中获取尿液样本：30例膀胱癌患者、15例非恶性膀胱疾病患者和8名健康个体。通过逆转录实时PCR测量hTERT mRNA。使用针对3号、7号、17号染色体着丝粒区域的荧光标记探针混合物以及针对9p21位点的位点特异性标识符p16探针进行M-FISH。我们证明，血红蛋白试纸条、BTA和FDP检测的总体敏感性略高于尿液细胞学检查，但特异性较低。与尿液细胞学检查相比，hTERT mRNA表达标志物在检测所有膀胱癌，尤其是浅表性和低级别肿瘤方面具有显著更高的敏感性，且特异性更高。在检测膀胱肿瘤方面，M-FISH比尿液细胞学检查显著更敏感，但特异性较低（结果不显著）。在检测低分期和低级别肿瘤方面比较这两种检测方法时，M-FISH的卓越敏感性得以保持。在检测肿瘤复发方面，M-FISH是最敏感和特异的检测方法，其次是BTA检测。在随访期间，hTERT、血尿筛查和FDP显示出相对较低的敏感性和特异性。我们的研究结果表明，评估尿液中的hTERT表达和染色体异常是可靠的工具——与传统细胞学检查同样特异，但敏感性远高于传统细胞学检查——可用于早期检测膀胱癌。FISH在检测复发方面的高敏感性使其有助于减少在这些病例的精确随访中通常进行的膀胱镜检查次数。
