[Correlation of genetic and cytogenetic alterations in pathological aggressiveness urothelial carcinoma of the bladder: Performance of BCA-1, a mini-array comparative genomic hybridisation-based test]

Abstract

Introduction: Urothelial carcinomas are the fourth leading cause of cancer in humans. Their incidence is increasing by more than 50% in 25 years. The superficial forms (70% cases) require a close active surveillance to identify frequent recurrences and progression to invasive stage. Our main goal was to identify prognostic molecular markers for bladder cancer that could be used alone or in combination in routine clinical practice. In this aim, we evaluated the capability of the BCA-oligo test based on a CGH array to correctly classify tumoral grade/stage.

Method: Urinary DNA was extracted from 81 patients with superficial bladder cancer and has been hybridized on the BCA-oligo array. The results from the molecular analysis were correlated with the tumoral grade and stage.

Results: Several chromosomal alterations were significantly more frequent in tumors of higher grade and more advanced stage. A significant association was observed between a high grade and the presence of one of these alterations: loss on 6p, gain on 8q or 13q, loss or gain on 9q or 11q, with an odds ratio of 6.91 (95% CI=2.20-21.64; P=0.0009). Moreover, a significant association was found between a more advanced stage (pT1) and the presence of one of these alterations: loss on 6p, gain on 8q, loss or gain on 5p, with an odds ratio of 15.2 (95% CI=3.71-62.58; P=0.0002).

Conclusion: Our results showed that molecular analyses of superficial bladder cancers based on urinary DNA and the BCA-oligo test could be used as prognostic factor for the tumor evolution, allowing then a more adapted clinical management.

Keywords: Altérations cytogénétiques; Biomarkers; Biomarqueurs; Bladder cancer; Cancer de vessie; Comparative genomic hybridization; Cytogenetic alterations; Genetic chip; Hybridation génomique comparative; Puce génétique.