[DNA methylation on urinalysis and as a prognostic marker in urothelial cancer of the bladder].
OBJECTIVE
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.
Friedrich
M G
MG
Klinik und Poliklinik für Urologie, Universität Hamburg,Universitätsklinikum Hamburg Eppendorf, Hamburg. friedrich@uke.uni-hamburg.de
Toma
M I
MI
Chun
J K H F
JK
Steuber
T
T
Budäus
L
L
Isbarn
H
H
Huland
H
H
D014408:Biomarkers, Tumor; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016482:Urinalysis / Q000379:methods*; D001749:Urinary Bladder Neoplasms
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005819:Genetic Markers; D009363:Neoplasm Proteins