Contenu en ADN par cytométrie en flux et cytologie dans le diagnostic et le pronostic des tumeurs vésicales : résultats préliminaires d'une étude comparative sur lavage de la vessie

In order to determine if patients with a history of previous urothelial cell carcinoma (UCC) but with current normal urinary cytology have DNA damage in urothelial cells, the single-cell gel electrophoresis (comet) assay was conducted with cells obtained by urinary bladder washings from 44 patients (28 with a history of previous UCC). Increased DNA damage was observed in cytologically "normal" urothelial cells of patients with a history of UCC when compared with referents with no similar history and after correcting the data for smoking status and age (P < 0.018). Increased DNA damage also correlated with the highest tumor grade, irrespective of time or course of the disease after clinical intervention (Kendall tau correlation, 0.37, P = 0.016). Moreover, aneuploidy, as assessed by DNA content ratio (DCR; 75th/25th percentile of total DNA fluorescence of 50 comets/patient) was unaltered by smoking status, but increased with UCC grade: 1.39 +/- 0.12 (median +/- 95% confidence interval; referents); 1.43 +/- 0.11 (Grade I UCC; P = 0.264, against referents); 1.49 +/- 0.16 (Grade II UCC; P = 0.057); 1.57 +/- 0.16 (Grade III UCC; P = 0.003). Micronucleated urothelial cells (MNC) were also scored on Giemsa-stained routine cytological smears and were found not to correlate with DNA damage or DCR. MNC frequencies were higher for patients with a history of UCC and/or smoking than referents with neither history, but there was no statistical difference between groups. Taken together, these results suggest that the normal-appearing urothelium of patients resected for UCC still harbor genetically unstable cells.

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DNA damage in cytologically normal urothelial cells of patients with a history of urothelial cell carcinoma

Gontijo

Marcondes

Elias

et al. 2002

Environ and Mol Mutagen

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Molecular Pathology of Bladder Cancer

Netto

2012

Surgical Pathology Clinics

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Molecular biomarkers in urothelial carcinoma of the bladder: are we there yet?

Netto

2011

Nat Rev Urol

114

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The unprecedented advances in cancer genetics and genomics are rapidly affecting the clinical management of solid tumors. Molecular diagnostics are now an integral part of routine clinical management for patients with lung, colon, and breast cancer. In sharp contrast, molecular biomarkers have been largely excluded from current management algorithms for urologic malignancies. The need for new treatment options that can improve upon the modest outcomes currently associated with muscle-invasive bladder cancer is evident, and validated prognostic molecular biomarkers that can help clinicians to identify patients in need of early, aggressive management are lacking. Robust predictive biomarkers that are able to forecast and stratify responses to emerging targeted therapies are also needed.

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Contenu en ADN par cytométrie en flux et cytologie dans le diagnostic et le pronostic des tumeurs vésicales : résultats préliminaires d'une étude comparative sur lavage de la vessie

Cited by 6 publications

References 19 publications

DNA damage in cytologically normal urothelial cells of patients with a history of urothelial cell carcinoma

DNA damage in cytologically normal urothelial cells of patients with a history of urothelial cell carcinoma

Molecular Pathology of Bladder Cancer

Molecular biomarkers in urothelial carcinoma of the bladder: are we there yet?

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