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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

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Author(s):
Negraes, Priscilla D. [1, 2] ; Favaro, Francine P. [2] ; Camargo, Joao Lauro V. [1] ; Oliveira, Maria Luiza C. S. [1] ; Goldberg, Jose [3] ; Rainho, Claudia A. [2] ; Salvadori, Daisy M. F. [1]
Total Authors: 7
Affiliation:
[1] Sao Paulo State Univ, UNESP, Botucatu Med Sch, Dept Pathol, BR-18618000 Botucatu, SP - Brazil
[2] Sao Paulo State Univ, UNESP, Biosci Inst, Dept Genet, BR-18618000 Botucatu, SP - Brazil
[3] Sao Paulo State Univ, UNESP, Botucatu Med Sch, Dept Urol, BR-18618000 Botucatu, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BMC CANCER; v. 8, AUG 14 2008.
Web of Science Citations: 32
Abstract

Background: Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence. Methods: A set of 4 genes, including CDH1 (E-cadherin), SFN (stratifin), RARB (retinoic acid receptor, beta) and RASSF1A (Ras association (RalGDS/AF-6) domain family 1), had their methylation patterns evaluated by MSP (Methylation-Specific Polymerase Chain Reaction) analysis in 49 fresh urinary bladder carcinoma tissues (including 14 cases paired with adjacent normal bladder epithelium, 3 squamous cell carcinomas and 2 adenocarcinomas) and 24 cell sediment samples from bladder washings of patients classified as cancer-free by cytological analysis (control group). A third set of samples included 39 archived tumor fragments and 23 matched washouts from 20 urinary bladder cancer patients in post-surgical monitoring. After genomic DNA isolation and sodium bisulfite modification, methylation patterns were determined and correlated with standard clinic-histopathological parameters. Results: CDH1 and SFN genes were methylated at high frequencies in bladder cancer as well as in paired normal adjacent tissue and exfoliated cells from cancer-free patients. Although no statistically significant differences were found between RARB and RASSF1A methylation and the clinical and histopathological parameters in bladder cancer, a sensitivity of 95% and a specificity of 71% were observed for RARB methylation (Fisher's Exact test (p < 0.0001; OR = 48.89) and, 58% and 17% (p < 0.05; OR = 0.29) for RASSF1A gene, respectively, in relation to the control group. Conclusion: Indistinct DNA hypermethylation of CDH1 and SFN genes between tumoral and normal urinary bladder samples suggests that these epigenetic features are not suitable biomarkers for urinary bladder cancer. However, RARB and RASSF1A gene methylation appears to be an initial event in urinary bladder carcinogenesis and should be considered as defining a panel of differentially methylated genes in this neoplasia in order to maximize the diagnostic coverage of epigenetic markers, especially in studies aiming at early recurrence detection. (AU)