Comparison of telomerase activity and matrix metalloproteinase-9 in voided urine and bladder wash samples as a useful diagnostic tool for bladder cancer.

Abstract

This study was undertaken to evaluate the diagnostic efficacy of telomerase in urine, and bladder wash and also the matrix metalloproteinase-9 (MMP-9) in urine, compared with voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells. A total of 110 subjects provided a single preoperative voided morning urine sample for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. Cystoscopy was done for all patients as the reference standard for the identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the remaining 16 had benign urological disorders. A group of 21 healthy volunteers were also enrolled in this study. The optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 were calculated by receiver-operator characteristics (ROC) curves as 0.05, 0.088 and 0.51 (ng/ml), respectively. The levels and the positivity rates of the 2 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group, telomerase activity in urine, bladder wash, and MMP-9 were positive in 92%, 87% and 61%, respectively in bladder cancer patients with positive cytology. Moreover, these positive rates for them were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%, respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase activity in urine, and in bladder wash, respectively; 66.6% and 80% for MMP-9 and 58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher than either combined sensitivity of VUC with one of the biomarkers or than that of the biomarker alone. Our data indicate that urinary telomerase and MMP-9 had superior sensitivities over VUC. The combined use of markers increased the sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers in bilharzial bladder cancer than non-bilharzial type highlight their clinical utility in screening patients with urinary bilharziasis.