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Acta Cytol. 2006 Sep-Oct;50(5):499-506.

Methylation profiling of urothelial carcinoma in bladder biopsy and urine.

Author information

1
Department of Pathology, Division of Cytopathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. robertpu@umich.edu

Abstract

OBJECTIVE:

To test DNA methylation profiling in detection of urothelial carcinoma in urine.

STUDY DESIGN:

Thirty-three bladder specimens were analyzed for the DNA p16INK4a, 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 andfound 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 p14ARF, p16INK4a, RASSF1, GSTP and E-Cad had similar methylation profiles.

CONCLUSION:

These results suggest that methylation of p14ARF, p16INK4a, 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.

PMID:
17017434
DOI:
10.1159/000326003
[Indexed for MEDLINE]

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