Detection of bladder cancer from the urine using fluorescencein situ hybridization technique

Abstract

The authors report on their first experiences with the UroVysion fluorescence in situ hybridization (FISH) kit developed for the detection of bladder cancer. This new non-invasive diagnostic application of the FISH technique in the field of urology was elaborated to replace cystoscopy. The special urine examination method detects genetic alterations of the urothelial cells found in the urine, using fluorescent directlabeled DNA probes binding to the peri-centromeric regions of chromosomes 3, 7 and 17 as well as on the 9p21 locus. We aimed to evaluate the utility of UroVysion test in the light of the histological diagnosis. Urine samples from 43 bladder cancer patients and 12 patients with no or benign alterations were studied using a new application of FISH technique: the UroVysion reagent kit. The obtained FISH results were compared with the histological findings of the transurethral surgical resection specimens. The study rated the specificity and sensitivity of the technique 100% and 87%, respectively. Therefore, the technique could well fit into the diagnostic process of bladder carcinomas. Statistical analyses showed significant correlation between tumor progression and the severity of the genetic alterations detected by this FISH technique. Furthermore, positive correlation was found between tumor grade and the proportion of tumor cells showing genetic abnormality. The noninvasiveness, the robustness of evaluation and the high specificity/sensitivity are all in favor of this technique. The disadvantages are the higher costs of the technical background and the required future clinical studies to determine whether this technique can replace cystoscopy.

Automated signal pattern evaluation of a bladder cancer specific multiprobe‐fish assay applying a user‐trainable workstation

“…In addition, there is lack of consensus regarding (i) diagnostic cut-off, (ii) interpretation of scoring results, and (iii) number of cells to be analyzed. Furthermore, several groups have noted its ambiguity regarding current target definition and thus association with certain drawbacks of conventional cytology (Bubendorf, 2007;Daniely et al, 2005;Lokeswhar et al, 2005;Pycha, 2007;Riesz et al, 2007).…”

Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus

“…After removal of reviews, meta-analyses, and redundant trials, 21 studies assessable for criteria concerning assay performance and comprising 2,852 individuals were identified, forming the basis for this assessment of assay performance [18,34,35,36,84,86,87,88,89,90,91,95,118,119,120,121,122,123,124,125,126,127]. …”

Urovysion: Considerations on modifying current evaluation scheme, including immunophenotypic targeting and locally set, statistically derived diagnostic criteria

“…The manufacturer gives guidelines, advising ORIGINAL ARTICLE abnormal DAPI morphology for targeting and preset absolute values for diagnostic cut-off, but interestingly many workgroups try to modify these criteria. Modifications include slight (11,12) or notable (24,25) changing of the recommended absolute cut-off values, partial (14,25,26) or comprehensive (13,27,28) application of percentage-based evaluation, or the use of new targeting approaches due to observations that DAPI morphology related targeting could be misleading (16). Because the number of analyzed cells varies and some of these studies fail to describe unambiguous motivation behind modified evaluation strategies, results are inconsistent and comparison is difficult (9).…”

“…Another uncertainty is the non-objective target definition (14). Voided urine is often compromised by degenerative changes, contamination of vaginal cells (14,15), inflammatory cells and granulocytes, making evaluation difficult.…”

“…Voided urine is often compromised by degenerative changes, contamination of vaginal cells (14,15), inflammatory cells and granulocytes, making evaluation difficult. Standard targeting is based on fluorescent counterstain [(4' ,6-diamidino-2-phenylindole (DAPI)] related nuclear morphology.…”