Deletion of 9p21 in urine specimens collected from patients with a history of hematuria and bladder cancer

Abstract

11038 Background: Fluorescence in situ hybridization (FISH) of voided urine sediment is a sensitive and specific test for the detection of urothelial carcinoma. Common bladder cancer FISH testing consists of 4 DNA probes to chromosomes 3, 7, and 17 and band 9p21. The pattern of enumeration anomalies for these 4 DNA probes are not well documented. We sought to determine the incidence of chromosomal anomalies detected by these 4 probes in urine specimens. Methods: Urine samples from a total of 13,284 patients with a history of hematuria and/or bladder cancer were included for study. FISH was performed in each case using fluorescence-labeled probes to the pericentromeric regions of chromosomes 3, 7, and 17 and band 9p21; cytology was also performed in all cases. Follow-up bladder biopsy information was collected from 280 cases. Results: In total, 91.6% (12163/13284) of urine samples were sufficient for FISH analysis. The overall FISH positive rate was 5.7% (691/12163), and the most frequent patterns of chromosomal anomalies were gains of chromosomes 3 and 7 (56.5%), 7 and 17 (51.6%), and 3 and 17 (36.9%). Deletion of 9p21 was observed in only 12% of cases, and was never observed as the only chromosomal anomaly. The mean number of positive cells in FISH-positive cases was 8.8 (range 4–22). Among 280 cases with matching bladder biopsies, 178 (63.6%) had urothelial carcinoma. FISH was more sensitive than cytology for the detection of urothelial carcinoma (77.4% vs. 53.5%, respectively) (p= 0.03), but there was no significant difference in specificity (68% vs. 71.6%, respectively) (p> 0.05). Conclusions: Gains of chromosomes 3 and 7 by FISH were the most common enumeration anomalies in urine specimens, while deletion of 9p21 only was rare and never seen isolation. FISH was significantly more sensitive than cytology for the detection of urothelial carcinoma with equivalent specificity. No significant financial relationships to disclose.