Journal
ACTA CYTOLOGICA
Volume 50, Issue 5, Pages 499-506Publisher
KARGER
DOI: 10.1159/000326003
Keywords
cancer; urothelial; tumor suppressor genes; methylation; multiplex MSP
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Objective To test DNA methylation profiling in detection of urothelial carcinoma in urine. Study Design Thirty-three bladder specimens were analyzed for the DNA methylation status of p(14ARF), p(16INK4a), RASSF1, APC, GSTP, E-Cad and CyclinD2 genes to determine if there is a difference in gene methylation between benign and malignant cases. Urine samples were analyzed in a feasibility study. Finally, methylation profiles of urine samples were obtained and compared with follow-up biopsy diagnoses. Results We found methylated genes in 18% benign, 37% urothelial carcinoma in situ and 93% infiltrating urothelial carcinoma cases (p = 0.001). Methylation profiles from the 18 urine samples revealed a significantly higher prevalence of methylated genes in carcinoma cases than benign cases (100% vs. 50%, p=0.025). We analyzed methylation profiles in 37 cytologically atypical urine samples with malignant or benign diagnosis on surgical follow-up and found that only APC (55% in malignant vs. 0% in benign, p=0.025) and CyclinD2 were differentially methylated (35% in malignant vs. 0% in benign, p=0.2) while p(14ARF), p(16INK4a), RASSF1, GSTP and E-Cad had similar methylation profiles. Conclusion These results suggest that methylation of p(14ARF), p(16INK4a), RASSF1, GSTP and E-Cad genes may not accurately identify carcinoma, but methylated APC and CyclinD2 might be useful biomarkers for urothelial carcinoma in urine.
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