Multiprobe Fluorescence in situ Hybridization (UroVysion) for the Detection of Urothelial Carcinoma – FISHing for the Right Catch

Abstract

Urinary cytology has a well-established role in the detection and monitoring of urothelial carcinoma. The main strength of cytology is the high specificity for high-grade urothelial carcinoma and carcinoma in situ, but it has a low sensitivity for low-grade, non-invasive tumors. There are several other limitations of cytology. Cytology of the upper urinary tract and after intravesical therapy with bacillus Calmette-Guerin is notoriously difficult to interpret. In addition, there is a poorly defined but commonly used category of atypical cytology of uncertain significance. The UroVysion multiprobe fluorescence in situ hybridization has emerged as a helpful tool to address these limitations. It consists of fluorescently labeled DNA probes to detect increased copy numbers (polysomy) of the chromosomes 3, 7 and 17 and deletion of 9p21, the site of the P16 tumor suppressor gene. Multiple studies have shown that fluorescence in situ hybridization in voided urine and washing specimens can help in patient management due to its superior sensitivity over cytology in different situations. It can be particularly useful to clarify equivocal cytological findings. However, some aspects remain to be further addressed including cost efficiency, optimal cut-off values and the true performance under real-life conditions.

What are the currently available and in development molecular markers for bladder cancer? Will they prove to be useful in the future?

“…[36] Nevertheless, compared to urine cytology, the routine use of UroVysion is still debatable; this test is a costly method to diagnose clinically insignificant low-grade bladder tumors. [37,38] In addition, the false positive rate related to the presence of benign urothelial umbrella cells with abnormal DNA ploidy makes the routine use of UroVysion relatively unfavorable. [39] Microsatellite analysis has been described in the literature since 1997, and its role in detecting low-grade non-invasive bladder cancer has been evaluated.…”

Diagnostic utility of double immunostaining of a urine cytology preparation for cytokeratin 20/p53 expression in a young woman with micropapillary urothelial carcinoma of the renal pelvis presenting as an unknown primary malignancy

“…[4] Therefore, several additional urinary cytological assessments have been developed over the last 20 years to improve the detection rate of UC. These include fluorescence in situ hybridization (FISH)[5] for the detection of chromosomal aberrations (loss of the 9p21 locus, which is the site of the p16 tumor suppressor gene, has been identified as a common chromosomal aberration in patients with UC) and an immunocytology test (uCyt+ test),[6] which combines conventional urine cytology and an immunofluorescence assay using a cocktail of antibodies against UC-associated surface antigens such as carcinoembryonic antigen and mucin-like glycoprotein. Furthermore, protein-based tests such as the quantitative nuclear matrix protein 22-enzyme-linked immunoadsorbent assay (NMP22-ELISA)[7] have become widely available and are frequently used by specialized centers and practitioners.…”

Distinguishing Urothelial Carcinoma in the Upper Urinary Tract from Benign Diseases with Hematuria Using FISH

“…Studies have shown that fluorescently labeled probes of chromosomes 3, 7, 17 and 9 could detect bladder UC as a non-invasive and sensitive test [5,6,7,9,10,14,15,16,17,18,19,20,21,22]. To date, few groups reported their studies on the utility of FISH in the detection of UUT-UC [23,24,25].…”