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.
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: Eli Rosenbaum; Mohammad Obaidul Hoque; Yoram Cohen; Marianna Zahurak; Mario A Eisenberger; Jonathan I Epstein; Alan W Partin; David Sidransky Journal: Clin Cancer Res Date: 2005-12-01 Impact factor: 12.531
Authors: Frank Christoph; Steffen Weikert; Carsten Kempkensteffen; Hans Krause; Martin Schostak; Kurt Miller; Mark Schrader Journal: Int J Cancer Date: 2006-09-15 Impact factor: 7.396
Authors: Mohammad Obaidul Hoque; Shahnaz Begum; Ozlem Topaloglu; Aditi Chatterjee; Eli Rosenbaum; Wim Van Criekinge; William H Westra; Mark Schoenberg; Marianna Zahurak; Steven N Goodman; David Sidransky Journal: J Natl Cancer Inst Date: 2006-07-19 Impact factor: 13.506
Authors: Martin G Friedrich; Angelika Hellstern; Stefan H Hautmann; Markus Graefen; Stefan Conrad; Edith Huland; Hartwig Huland Journal: J Urol Date: 2002-08 Impact factor: 7.450
Authors: Marieta I Toma; Martin G Friedrich; Stefan H Hautmann; K Thorsten Jäkel; Andreas Erbersdobler; Angelika Hellstern; Hartwig Huland Journal: World J Urol Date: 2004-02-27 Impact factor: 4.226