The Value of Combined Use of Survivin mRNA and Matrix Metalloproteinase 2 and 9 for Bladder Cancer Detection in Voided Urine

Objective: In a trial to improve the diagnostic efficacy of conventional urine cytology we determine survivin RNA and matrix metalloproteinase 2 and 9 in urine of bladder cancer cases. Method: Voided urine specimens were collected from patients with histologically confirmed bladder urothelial carcinoma (Group 1; n = 46), urological patients without urothelial carcinoma (Group 2; n = 20), and healthy volunteers (Group 3; n = 20). Urine cytology, survivin RNA was estimated by qualitative nested RT-PCR and MMP-2, MMP-9 activity were detected by gelatin zymography. The expression of survivin RNA and matrix metalloproteinase 2 and 9 in bladder cancer was compared with benign and normal cases. Results: Positivity rates of survivin RNA and MMPs zymography were significantly different among the 3 groups. Urine survivin detection by qualitative nested RT-PCR showed 76.1% sensitivity and 95% specificity. The overall sensitivity, specificity of urinary MMP zymography was 67.3%, 90% respectively. The combined use of urine cytology with urine survivin or MMPs zymography increased sensitivity of urine cytology from 50% to 84.7%. The highest sensitivity (95.6%) was obtained on combining the three markers. Conclusion: Survivin RNA and MMPS zymography can be considered as promising noninvasive markers for bladder cancer early detection. Combined use of the three markers improved the sensitivity for detecting bladder cancer.