Methylation profiling of urothelial carcinoma in bladder biopsy and urine

Robert T. Pu, Lauren E. Laitala, Douglas P. Clark

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To test DNA methylation profiling in detection of urothethial carcinoma in urine. Study Design: Thirty-three bladder specimens were analyzed for the DNA methylation status of p14ARF, 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 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 p14ARF, p16INK4a, RASSF1, GSTP and E-Cad had similar methylation profiles. Conclusion: These results suggest that methylation of p14ARF, p16INK4a, RASSFl, GSTP and E-Cad genes may not accurately identify carcinoma, but methylated APC and CyclinD2 might be useful biomarkers for urothelial carcinoma in urine.

Original languageEnglish (US)
Pages (from-to)499-506
Number of pages8
JournalActa cytologica
Volume50
Issue number5
DOIs
StatePublished - Jan 1 2006

Keywords

  • Cancer
  • Methylation
  • Multiplex MSP
  • Tumor suppressor genes
  • Urothelial

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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