Abstract
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.
Highlights
Bladder carcinoma is one of the most common urologic malignancies occurring worldwide [1]
Qualitative RT-PCR and MMPs zymography in 46 samples revealed positivity in 76.1% and 67.4%, respectively, of the malignant group and in 10% and 20% of the benign group and not detected in normal individuals (p < 0.001, Table 1)
Sensitivity of urine cytology improved when combined with survivin RNA or MMPs zymography while the best sensitivity for urine cytology was achieved when the 3 markers were combined (Table 3)
Summary
Bladder carcinoma is one of the most common urologic malignancies occurring worldwide [1]. In Egypt it accounts for 30% of all cancers [2] and has been associated with many pathogenetic factors, most commonly bilharzial infestation [3]. Definitive proof of bladder cancers requires invasive cystoscopic examinations. This procedure is uncomfortable and laborintensive, in follow-up [4]. New, noninvasive methods for bladder cancer detection would open new possibilities in diagnosis and monitoring [6], as well as in screening of groups at risk such as bilharzial infested patients [7,8,9]. An ideal test to monitor bladder cancer should be objective, noninvasive, easy to administer and interpret and have high sensitivity and specificity
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