Combined morphologic and fluorescence in situ hybridization analysis of voided urine samples for the detection and follow-up of bladder cancer in patients with benign urine cytology.

BACKGROUND: Bladder cancer is among the 5 most common malignancies worldwide. Patients with bladder cancer are closely followed with periodic cystoscopies and urine cytology analyses due to the significant risk of tumor recurrence. The UroVysion fluorescence in situ hybridization (FISH) test demonstrated higher sensitivity over urine cytology in detecting bladder cancer by most comparative studies. METHODS: In the current study, the diagnostic usefulness of a combined cytology and FISH analysis approach was tested using the Duet automatic scanning system in patients with benign urine cytology who were being monitored for recurrent urothelial carcinoma or being assessed for various urologic symptoms. RESULTS: By combining the benefits of conventional cytology with molecular diagnostics, a more sensitive detection of bladder cancer was attained. All patients who had positive cystoscopy concomitantly with urine sampling were detected by combined analysis. Additional patients that developed transitional cell carcinoma during a follow-up period of 24 months had a previous positive result on combined analysis. Only 2 patients with a negative combined analysis result presented with late disease recurrence (20 months and 22 months, respectively, after the negative test). Therefore, negative combined analysis was found to be predictive of a lack of disease recurrence for at least 12 months. In this timeframe, the overall sensitivity, specificity, negative predictive value (NPV), and positive predictive values of the combined analysis test were 100%, 65%, 100%, and 44%, respectively. CONCLUSIONS: Given the absolute sensitivity and NPV of the combined analysis test, the management of patients with a negative combined analysis result might be revised and allow for more flexible assessment and management of bladder cancer patients relying more on urine bound tests.

Combined analysis of morphology and fluorescence in situ hybridization significantly increases accuracy of bladder cancer detection in voided urine samples.

OBJECTIVES: To evaluate a combined analysis approach that involves cytologic evaluation and fluorescence in situ hybridization analysis for detecting cancer cells in voided urine samples using an automated scanning station. METHODS: Voided urine samples from 41 patients suspected of having transitional cell carcinoma were stained with May-Grünwald Giemsa stain, scanned for atypical or suspicious cells, destained, and hybridized with a mixture of fluorescent-labeled probes. Samples were tested using either the UroVysion probe or by a mix of chromosomes 3, 7, and 17 centromeric probes. A case was regarded as positive when at least one cell was abnormal in both aspects, morphology and fluorescence in situ hybridization. Patients were evaluated concomitantly by cytology, cytoscopy, and biopsy, if indicated. RESULTS: Overall, 26 samples were positive by combined analysis. Biopsy-proven transitional cell carcinoma was positive by combined analysis in all cases (100%) and in 13 cases (61.9%) by cytology (P = 0.0133). The advantage of the combined analysis was noted mostly in low-grade and superficial tumors for which the sensitivity of cytology reached 30% (P = 0.023) and 27.27% (P = 0.0133), respectively. Specificity was 100%. CONCLUSIONS: Our results have shown that combined analysis for the presence of transitional cell carcinoma cells is a powerful tool, providing high sensitivity and specificity, and may offer a new scheme for bladder cancer management.