Detection of bladder cancer in urine sediments by a hypermethylation panel of selected tumor suppressor genes

BACKGROUND: Promoter hypermethylation can be a useful biomarker for early detection and prognosis of bladder cancer, monitoring response to treatment and complement classical diagnostic procedures. OBJECTIVE: The molecular test was performed on DNA from bladder cancer cells in voided urine samples, tumor tissue DNA and normal control DNAs. We aimed to assess the diagnostic potential of epigenetic changes in urine DNA from bladder cancer cases at various clinico-pathological stages of the disease. METHODS: The methylation status of 5 genes (p14ARF, p16INK4A, RASSF1A, DAPK, APC) in 113 tumor samples paired with voided urine specimens was analyzed by MSP. We compared the results of methylation analysis with UroVysion test. RESULTS: The methylation profile in tumor/urine DNA was significantly correlated (p ≤ 0,05) with tumor grade in p14ARF, RASSF1a, APC/p14ARF, APC genes, respectively and with stage in p14ARF, RASSF1a/p14ARF genes, respectively. The results of UroVysion test were in correlation with hypermethylation both in tumor and urine DNA in p14ARF, RASSF1a and APC genes (p = 0,008; 0,02 and 0,04, respectively). CONCLUSIONS: Promoter hypermethylation of tumor suppressor genes is a frequent mechanism in bladder cancer. We found promoter hypermethylation in all grades and stages of all cases examined. Methylation profile of selected suppressor genes may be a potential useful biomarker and enhance early detection of bladder cancer using a noninvasive urine test.