The detection of urinary HYAL1 and survivin RNA is a promising noninvasive test for bladder cancer early detection. HYAL1 RNA was more sensitive and specific than urine cytology. Semiquantitative reverse transcriptase-polymerase chain reaction is favored for its high sensitivity and specificity.

Background: Bladder cancer cells illustrate major disruptions in their DNA methylation patterns as compared with normal ones. Authors aimed to identify epigenetic molecular markers in urine for early detection of bladder cancer.Materials and Methods: We retrospectively analyzed the methylation status of RARb 2 and APC genes in urine samples from 210 bladder cancer patients, 61 patients with benign urological diseases, and 49 healthy volunteers by using methylation-specific PCR.Results: Methylated RARb 2 and APC were significantly higher in bladder cancer patients (62.8%, 59.5%) than benign (16.4%, 5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathologic factors; however, they were detected in all grades and stages. Among the 128 patients with bilharzial bladder cancer, 94 (73.4%) showed methylated RARb 2 and 86 (67.2%) showed methylated APC. Homoplasmic methylation pattern of both genes were only detected in bilharzial bladder cancer cases. Both sensitivities and specificities of the methylated genes for bladder cancer detection were superior to urine cytology and when altogether combined, the sensitivities improved to (91.8%), (93.5%), (91.9%), and (80.9%) in detection of: bladder cancer, non-muscle invasive bladder cancer, low-grade tumors, and bilharzial associated bladder cancer, respectively.Conclusion: Thus, methylated RARb 2 and APC genes might be valuable urinary molecular markers for early detection of bilharzial and nonbilharzial bladder cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1657-64. Ó2011 AACR.

BACKGROUNDA new, sensitive, noninvasive method for the detection of urothelial carcinomas of the urinary bladder would open new possibilities in both the diagnosis and followup of patients.METHODSThis study included 228 patients diagnosed with bladder carcinoma, 68 patients with benign bladder lesions, and 44 healthy persons served as the control group. All were subjected to: serologic schistosomiasis antibody assay in serum, urine cytology, estimation of urine hyaluronic acid (HA) by enzyme‐linked immunosorbent assay, and detection of CK‐20 and hyaluronidase (HAase) by reverse transcription polymerase chain reaction (RT‐PCR) in urothelial cells from voided urine.RESULTSHA mean rank was higher in benign and malignant groups than in the healthy group (P < 0.0001) and was significantly related to tumor grade (P = 0.021). HA best‐cutoff, determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups, was 58.5 units/mg protein at 85.8% sensitivity and 60.7% specificity. HAase RNA showed superior sensitivity (90.8%) over cytology (68.9%) and CK‐20 (78.1%) with specificity of 93.4%, 98.1% and 80.2%, respectively. The sensitivity reached 94.7% at a specificity of 91.5% when combined with CK‐20. All 4 of the investigated markers were related to grade at P <0.05. Whereas only HAase and CK‐20 were significantly related to stage (P < 0.05). As to schistosomiasis, only HAase RNA positivity was significantly associated (P = 0.038).CONCLUSIONSHAase RNA is a promising noninvasive test with high sensitivity and specificity in bladder carcinoma detection. Cancer 2005. © 2005 American Cancer Society.