title: Increased efficiency of detecting genetically aberrant cells by UroVysion test on voided urine specimens using automated immunophenotypical preselection of uroepithelial cells.
abstract: There is a steady search for procedure which could replace or at least reduce the frequency of the invasive cystoscopy in the surveillance of heterogeneous superficial transitional cell carcinoma (TCC) of the bladder. Recently, UroVysion FISH assay has been shown to provide with better sensitivity than the urine cytology except for the lowest stage pTa and grade I-II TCCs. Data indicate that this failure of the sensitive FISH might be due to mistargeting. Therefore, our aim was to elaborate a procedure enabling FISH analysis in phenotypically preselected urothelial cells, only. Cytokeratin 7 (CK-7) chromogenic immunolabeling was applied to various mixtures of negative and positive control cells as well as voided urine specimens. Cellular targets and CK-7 positive cells were identified by morphometric and pixel intensity indices using an automated microscope workstation. UroVysion FISH pattern was analyzed only in the subsequently relocalized CK-7 positive events. Automated phenotypical preselection of urothelial cells proved to have 97.3% sensitivity, 96.1% specificity, and 99.0% accuracy, whereas combined pheno- and genotyping revealed 93.3% sensitivity and 99.8% specificity, respectively. In clinical samples, the overall 20.4% FISH positivity gained by traditional target identification contrasted with the 55.6% positivity obtained by the combined method, by which the efficiency of identifying chromosomally aberrant cells proved to be two to threefold higher even in grade I lesions. FISH analysis of phenotypically preselected urothelial cells might represent a reliable asset in surveillance of low stage-low grade TCCs.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Pécs, Hungary.
authors.forename: Gabor
authors.initials: G
authors.lastname: Pajor
authors.forename: Norbert
authors.initials: N
authors.lastname: Sule
authors.forename: Donat
authors.initials: D
authors.lastname: Alpar
authors.forename: Bela
authors.initials: B
authors.lastname: Kajtar
authors.forename: Maria
authors.initials: M
authors.lastname: Kneif
authors.forename: Daniel
authors.initials: D
authors.lastname: Bollmann
authors.forename: Laszlo
authors.initials: L
authors.lastname: Somogyi
authors.forename: Laszlo
authors.initials: L
authors.lastname: Pajor
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology* / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D001743:Urinary Bladder / Q000166:cytology* / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor