The Diagnostic Efficacy of Urinary Survivin and Hyaluronidase mRNA as Urine Markers in Patients with Bladder Cancer

Background: A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the bladder would open new possibilities in both the diagnosis and follow up of patients. Methods: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1: n = 60), urological patients without urothelial carcinoma (Group 2: n = 20), and healthy volunteers (Group 3: n = 20). All underwent serological assessment of schistosomiasis antibody, quantitative measurement of survivin by ELISA in urine supernatant, urine cytology, and detection of hyaluronidase (HYAL-1) by RT-PCR in urothelial cells of voided urine samples. Results: Urinary survivin mean rank was higher in malignant and benign groups than in the healthy group (p < 0.001). Urinary survivin best-cutoff was determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups (2537.25 pg/mg protein) at 78.33% sensitivity and 82.5% specificity. HAase mRNA showed superior sensitivity (86.67%) over cytology (38.33%) and urinary survivin (78.33%) with specificity of 97.5%, 100%, and 82.5%, respectively. The sensitivity of urine cytology was increased on combination with either survivin (83.33%) or HAase (90%). Also, the combination of both markers increased overall sensitivity (95%). Conclusions: Survivin can be reliably and quantitatively measured in urine of bladder cancer patients, improving the sensitivity and specificity of urine cytology for the diagnosis of bladder cancer. Combined use of cytology with survivin and HAase was the best recommended combination for bladder cancer detection.