[DNA Methylation on Urinalysis and As a Prognostic Marker in Urothelial Cancer of the Bladder]

Overview

Journal Urologe A

Specialty Urology

Date 2007 May 25

PMID 17522834

Citations 3

Authors

M G Friedrich

M I Toma

J K H F Chun

T Steuber

L Budaus

H Isbarn

H Huland

Affiliations

Soon will be listed here.

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.

Citing Articles

The Development of Non-Invasive Diagnostic Tools in Bladder Cancer.

Schulz A, Loloi J, Martina L, Sankin A Onco Targets Ther. 2022; 15:497-507.

PMID: 35529887 PMC: 9075009. DOI: 10.2147/OTT.S283891.

Trends in urine biomarker discovery for urothelial bladder cancer: DNA, RNA, or protein?.

Humayun-Zakaria N, Ward D, Arnold R, Bryan R Transl Androl Urol. 2021; 10(6):2787-2808.

PMID: 34295762 PMC: 8261432. DOI: 10.21037/tau-20-1327.

RASSF-1A modulates proliferation-mediated oral squamous cell carcinoma progression.

Sun J Cancer Cell Int. 2019; 19:213.

PMID: 31423110 PMC: 6693157. DOI: 10.1186/s12935-019-0932-9.

References

Esteller M, Corn P, Baylin S, Herman J . A gene hypermethylation profile of human cancer. Cancer Res. 2001; 61(8):3225-9. View

Tsujii M, DuBois R . Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell. 1995; 83(3):493-501. DOI: 10.1016/0092-8674(95)90127-2. View

Simon M, Lokeshwar V, Soloway M . Current bladder cancer tests: unnecessary or beneficial?. Crit Rev Oncol Hematol. 2003; 47(2):91-107. DOI: 10.1016/s1040-8428(03)00074-x. View

Toma M, Friedrich M, Hautmann S, Jakel K, Erbersdobler A, Hellstern A . Comparison of the ImmunoCyt test and urinary cytology with other urine tests in the detection and surveillance of bladder cancer. World J Urol. 2004; 22(2):145-9. DOI: 10.1007/s00345-003-0390-8. View

Friedrich M, Toma M, Hellstern A, Pantel K, Weisenberger D, Noldus J . Comparison of multitarget fluorescence in situ hybridization in urine with other noninvasive tests for detecting bladder cancer. BJU Int. 2003; 92(9):911-4. DOI: 10.1111/j.1464-410x.2003.04528.x. View

Christoph F, Weikert S, Kempkensteffen C, Krause H, Schostak M, Miller K . Regularly methylated novel pro-apoptotic genes associated with recurrence in transitional cell carcinoma of the bladder. Int J Cancer. 2006; 119(6):1396-402. DOI: 10.1002/ijc.21971. View

Hoque M, Begum S, Topaloglu O, Chatterjee A, Rosenbaum E, Van Criekinge W . Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst. 2006; 98(14):996-1004. DOI: 10.1093/jnci/djj265. View

Rosenbaum E, Hoque M, Cohen Y, Zahurak M, Eisenberger M, Epstein J . Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy. Clin Cancer Res. 2005; 11(23):8321-5. DOI: 10.1158/1078-0432.CCR-05-1183. View

Friedrich M, Hellstern A, Hautmann S, Graefen M, Conrad S, Huland E . Clinical use of urinary markers for the detection and prognosis of bladder carcinoma: a comparison of immunocytology with monoclonal antibodies against Lewis X and 486p3/12 with the BTA STAT and NMP22 tests. J Urol. 2002; 168(2):470-4. DOI: 10.1016/s0022-5347(05)64660-5. View

10.

Laird P . The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003; 3(4):253-66. DOI: 10.1038/nrc1045. View

11.

Jones P, Baylin S . The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002; 3(6):415-28. DOI: 10.1038/nrg816. View

12.

Narayan G, Arias-Pulido H, Koul S, Vargas H, Zhang F, Villella J . Frequent promoter methylation of CDH1, DAPK, RARB, and HIC1 genes in carcinoma of cervix uteri: its relationship to clinical outcome. Mol Cancer. 2003; 2:24. PMC: 156646. DOI: 10.1186/1476-4598-2-24. View

13.

Jones P, Laird P . Cancer epigenetics comes of age. Nat Genet. 1999; 21(2):163-7. DOI: 10.1038/5947. View

14.

Lokeshwar V, Soloway M . Current bladder tumor tests: does their projected utility fulfill clinical necessity?. J Urol. 2001; 165(4):1067-77. View

15.

Chan M, Chan L, Tang N, Lo K, Tong J, Chan A . Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients. Int J Cancer. 2003; 104(5):611-6. DOI: 10.1002/ijc.10971. View

16.

Bornman D, Mathew S, Alsruhe J, Herman J, Gabrielson E . Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals. Am J Pathol. 2001; 159(3):831-5. PMC: 1850472. DOI: 10.1016/S0002-9440(10)61758-0. View

17.

Schneider-Stock R, Boltze C, Lasota J, Miettinen M, Peters B, Pross M . High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors. J Clin Oncol. 2003; 21(9):1688-97. DOI: 10.1200/JCO.2003.08.101. View

18.

Eads C, Danenberg K, Kawakami K, Saltz L, Blake C, Shibata D . MethyLight: a high-throughput assay to measure DNA methylation. Nucleic Acids Res. 2000; 28(8):E32. PMC: 102836. DOI: 10.1093/nar/28.8.e32. View

19.

Chan M, Chan L, Tang N, Tong J, Lo K, Lee T . Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Clin Cancer Res. 2002; 8(2):464-70. View

20.

Liang G, Robertson K, Talmadge C, Sumegi J, Jones P . The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cells. Cancer Res. 2000; 60(17):4907-12. View