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Evaluation of fluorescence in situ hybridization as an ancillary tool to urine cytology in diagnosing urothelial carcinoma.

Our purpose was to evaluate the feasibility of performing fluorescence in situ hybridization (FISH) on routine urine samples and to compare the relative sensitivities of urine cytology and FISH for detecting urothelial carcinoma. Light microscopy (LM) using cytologic evaluation and FISH were used to study 121 consecutive urine samples. A mixture of fluorescent probes to chromosomes 3, 7, 17, and the 9p21 locus were used for detection of numerical chromosomal abnormalities (UroVysion, Vysis/Abbott). Biopsy specimens from patients in the study were reviewed if available. FISH analysis was performed without knowledge of cytology or biopsy findings. The urine cytology of 121 samples was interpreted as 59 negative, 41 reactive, 16 atypical, 2 suspicious and 3 insufficient cells for diagnosis. 85 samples were successfully analyzed by FISH. Thirty-one of these showed chromosomal abnormalities and these samples were initially regarded on the original cytology reading as follows: 10 negative, 10 reactive, 9 atypical, and 2 suspicious. FISH demonstrated chromosomal abnormalities in a significant number of cases (67%) that were initially diagnosed as normal or reactive by LM. Twenty-five patients were identified who had biopsy-proven TCC and successful FISH. Thirteen of the 25 patients (52%) were abnormal by FISH (cytology: 2 suspicious, 6 atypical, 4 reactive, 1 negative). One patient was atypical by cytology with normal FISH results but had TCC on biopsy. Hyperdiploidy for chromosomes 3 (77%) and 7 (67%) were seen consistently. Multiple chromosomal abnormalities were seen in 67% of these cases. We conclude that FISH has a greater sensitivity in detecting urothelial carcinoma when coupled with urine cytology. It is not entirely clear at this time whether a positive FISH may indicate frank neoplastic urothelial transformation or merely be an indicator of unstable urothelium capable of or primed for malignant transformation thus detecting patients at significant risk. The use of FISH in conjunction with urine cytology can potentially reduce urothelial carcinoma morbidity and mortality by diagnosing these tumors earlier.

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