Urinary retinoic acid receptor-β2 gene promoter methylation and hyaluronidase activity as noninvasive tests for diagnosis of bladder cancer

ObjectivesWe evaluated the significance of urinary retinoic acid receptor-β2 (RAR-β2) gene promoter methylation and hyaluronidase activity in comparison with voided urine cytology (VUC) in diagnosis of bladder cancer.Design and MethodsThis study included 100 patients diagnosed with bladder cancer, 65 patients with benign urological disorders and 51 healthy volunteers. Urine supernatant was used for determining hyaluronidase activity by zymography while urine sediment was used for cytology and detection of methylated RAR-β2 gene promoter by methylation specific nested PCR.ResultsThe sensitivity and specificity were 53% and 90.5% for VUC, 65% and 89.7% for percent methylation fraction of RAR-β2 gene promoter, and 89% and 90.5% for hyaluronidase activity; combination of the three parameters increased sensitivity to 95%. A significant association was observed between investigated markers and advanced grade tumor.ConclusionsCombined use of RAR-β2 gene promoter methylation, hyaluronidase activity and VUC is promising non-invasive tool for bladder cancer detection.

► The sensitivity of urinary hyaluronidase activity is superior to the sensitivity of urinary percent methylation fraction of RAR-β2 gene promoter and urine cytology for detection of bladder cancer. ► The positivity rates of urinary percent methylation fraction of RAR-β2 gene promoter, urinary hyaluronidase activity and urine cytology are higher in grade 3 than grades 1, 2 of bladder cancer. ► Combined use of urinary RAR-β2 gene promoter methylation, urinary hyaluronidase activity and urine cytology is promising non-invasive tool for bladder cancer detection.