[DNA methylation on urinalysis and as a prognostic marker in urothelial cancer of the bladder]

Urologe A. 2007 Jul;46(7):761-8. doi: 10.1007/s00120-007-1360-3.
[Article in German]

Abstract

Introduction and objectives: Detection of promoter hypermethylation has been proposed as a promising tool for cancer diagnosis and as a prognostic marker in various cancers. We studied the versatility of DNA methylation for noninvasive diagnosis and as a prognostic marker for non-muscle-invasive bladder carcinoma.

Methods: Tumor specimens were microdissected and DNA was extracted from 105 paraffin-embedded paraffin specimens from patients undergoing transurethral resection for non-muscle-invasive bladder carcinoma. Urine specimens were collected from patients undergoing cystectomy for bladder cancer and from healthy volunteers. Methylation status was assessed with the real-time quantitative methylation-sensitive PCR (MethyLight). We checked a panel of 20 cancer-associated genes (p14ARF, p16 CDKN2A, STAT-1, SOCS-1, DR-3, DR-6, PIG-7, BCL-2, H-TERT, BAX, EDNRB, DAPK, RASSF-1A, FADD, TMS-1, E-CADHERIN, ICAM-1, TIMP-3, MLH-1, COX-2) for DNA methylation.

Results: Follow-up data were available in 95 of 105 patients (91.4%). A tumor recurrence was observed in 26 patients (27.3%). We could identify six genes (SOCS-1, STAT-1, BCL-2, DAPK, TIMP-3, E-cadherin), where methylation was associated with tumor recurrence. In Kaplan-Meier analysis, TIMP-3 showed a significant association with recurrence-free survival. Methylation of TIMP-3 predicted prolonged disease-free interval. Regarding urinalysis we could identify a pattern of methylation markers including DAPK, BCL-2, and H-TERT that yielded a sensitivity of 81.1% with a specificity of 100% in a cancer-free control population

Conclusions: We present data on the clinical usefulness of methylation analysis in bladder carcinoma. Our data confirm that methylation analysis is a promising tool for bladder cancer diagnosis and prognosis.

Publication types

  • English Abstract

MeSH terms

  • Biomarkers, Tumor
  • DNA Methylation*
  • DNA, Neoplasm / genetics*
  • Female
  • Genetic Markers / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Polymerase Chain Reaction / methods*
  • Prognosis
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Urinalysis / methods*
  • Urinary Bladder Neoplasms

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Genetic Markers
  • Neoplasm Proteins