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

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.

• Authors: M G Friedrich, M I Toma, J K H F Chun, T Steuber, L Budäus, H Isbarn, H Huland
• Journal: Der Urologe. Ausg. A (Urologe A) Vol. 46 Issue 7 Pg. 761-8 (Jul 2007) ISSN: 0340-2592 [Print] Germany
• Vernacular Title: DNA-Methylierung in der Urindiagnostik und als Prognosemarker beim Urothelkarzinom der Harnblase.
• PMID: 17522834 (Publication Type: English Abstract, Journal Article)

Chemical References

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

Topics

• 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