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[315] The Utility of Fluorescence In Situ Hybridization for the Detection of Urothelial Carcinoma in Residual Urine Cytology Specimens with an Equivocal Diagnosis

BR Kipp, MB Campion, AH Zieman, AM Plagge, AJ Wendel, J Zhang, TJ Sebo, KC Halling. Mayo Clinic, Rochester, MN

Background: Urine cytology and cystoscopy are techniques used for detecting and monitoring patients for urothelial carcinoma (UC). The clinical management of patients with equivocal (atypical, suspicious, etc.) urine cytology diagnoses in the absence of clinically detectable tumor can be challenging since these patients often have, or ultimately develop UC. Fluorescence in situ hybridization (FISH) is a novel technique that utilizes fluorescently-labeled DNA probes to detect urinary cells with chromosomal abnormalities. The goal of this study was to determine the utility of FISH in the management of patients with an equivocal cytology diagnosis.
Design: Ninety-three residual urine samples from 74 males and 19 females (age 46-89 years; mean, 71 years) with a cytology diagnosis of atypical (N=50) or suspicious (N=43), same day cystoscopy result, and bladder biopsy within three months of the cytology diagnosis were collected and processed for FISH analysis. The FISH UroVysion probe set was used and specimens were considered positive by FISH if 4 cells demonstrated gains of two or more signals (polysomy) or if 20% of cells demonstrated homozygous 9p21 deletion.
Results: Forty-three (46%) of the 93 specimens analyzed were diagnosed as positive for malignancy by FISH (39 polysomy, 4 homozygous 9p21 deletion). Thirty-nine (91%) of these 43 patients had pathologic evidence of UC (10 pTa, 11 CIS, 2 T1, and 16 muscle-invasive tumors). Of the 4 remaining patients with a positive FISH result and negative biopsy, 1 patient had CIS on a follow-up biopsy, 1 had a follow-up positive cytology result, and the other two currently have no evidence of malignancy (follow-up time, 0 and 4 months). Fifty specimens were diagnosed as negative by FISH. Twenty-nine (58%) of these patients had negative biopsy results whereas the remaining 21 (42%) demonstrated biopsy proven UC staged as pTa (15), CIS (3), T1 (1), and T2 (2) tumors. FISH and cystoscopy alone detected 39/60 (65%) and 38/60 (63%) of cancers, respectively. When combined, 54/60 (90%) of patients with biopsy proven UC were identified. The six undetected tumors by both methodologies included 1pTaG1, 2pTaG2, 2 CIS, and 1 muscle-invasive UC with squamous differentiation.
Conclusions: The data from this study suggests that FISH, in conjunction with cystoscopy, may aid clinicians in the diagnosis of UC in patients with an equivocal cytology diagnosis.
Category: Cytopathology

Monday, March 26, 2007 11:30 AM

Platform Session: Section E, Monday Morning