Chromosomal instability and bladder cancer: the UroVysionTM test in the UroScreen study

What's known on the subject? and What does the study add? UroVysion™ is a multicolour fluorescence in situ hybridisation assay that detects DNA gain at chromosomes 3, 7 and 17 and loss at the 9p21 locus in exfoliated urothelial cells. This cell‐based test is time‐consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer. We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between DNA gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay. Objective To explore changes at chromosomes 3, 7, 17 and 9p21 in order to assess associations with bladder cancer for possible improvements of the UroVysion™ assay regarding screening. Subjects and Methods In all, 1609 men took part in the prospective study UroScreen. Annual screening for bladder cancer was offered to male chemical workers with former exposure to aromatic amines as a voluntary surveillance programme between 2003 and 2010. In all, 191 434 cells in 6517 UroVysion tests were analysed for copy number variations (CNV) at chromosome 3, 7, 17 (gains) and 9p21 (deletions) in 1595 men. We assessed CNVs at single or multiple loci using polysomy indices (PIs, called multiple PI and PI 3, PI 7 and PI 17). We calculated Spearman's rank correlation coefficients (rs) between these PIs and receiver operating characteristic (ROC) curves with areas under the curves (AUCs). We applied Cox regression to estimate hazard ratios (HRs) to assess the risk of developing bladder cancer. Results Nine out of 21 bladder tumours detected in 20 participants (‘cases’) had a positive UroVysion test, including seven high‐grade carcinomas and seven overlapping results with a positive cytology. Four cases with negative test results did not attend screening annually. No case was found because of a complete loss of 9p21 in at least 12 cells. There were strong correlations between pairwise combinations of gains at chromosome 3, 7 or 17, ranging between rs = 0.98 and rs = 0.99 in cases and between rs = 0.84 and rs = 0.88 in non‐cases (P < 0.001). Associations were less pronounced with CNVs at 9p21 among cases and were lacking in non‐cases. Estimates of the relative risk of DNA gain for developing a bladder tumour assessed wi