Diagnostic value of urinary molecular markers in bladder cancer

In an attempt to find a more sensitive and specific non-invasive diagnostic assay for the detection of bladder cancer cells, the authors assayed the exfoliated cells from patient's voided urine and bladder washing fluids for the presence of telomerase, an enzyme that maintains a cell's chromosomal length, metalloproteinase-9 (MMP-9), which has been associated with tumor cell invasion and metastasis. Their results were compared with both voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells.

The authors used preoperative voided morning urine samples from 110 subjects for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. 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. 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.

Receiver-operator characteristics (ROC) curves were used to determine the optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 [0.05, 0.088 and 0.51 (ng/ml), respectively]. The levels and the positivity rates of telomerase activity and MMP-9 were significantly higher in the malignant group compared to either the benign group or normal controls. Bladder cancer patients with positive cytology revealed positive telomerase activity in urine, bladder wash, and MMP-9 in 92%, 87% and 61%, respectively. Also, these positive rates 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, 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.

Urinary telomerase and MMP-9 had superior sensitivities over VUC; moreover, combined use of these 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.