Multiprobe FISH for Enhanced Detection of Bladder Cancer in Voided Urine Specimens and Bladder Washings
American Journal of Clinical Pathology
A b s t r a c t The aim of this study was to evaluate the UroVysion (Vysis, Downers Grove, IL) fluorescence in situ hybridization (FISH) test for improved detection of bladder cancer in urinary specimens. Three groups of specimens were examined, including voided urine specimens (1) collected before resection of bladder cancer, (2) from cystoscopically negative bladders of patients with previous bladder cancer, and (3) from patients with benign prostatic hyperplasia (controls). FISH positivity
... . FISH positivity was defined as more than 2 urothelial cells with an abnormal signal copy number of at least 1 of the 4 probes. FISH was positive in 1 of 27 control specimens and in 33 (73%) of 45 pTa, 12 (100%) of 12 pT1, and 13 (100%) of 13 pT2-4 tumors. The results were similar in a series of 68 bladder washings. In addition, FISH of voided urine specimens was positive in 5 of 10 patients with negative follow-up cystoscopy results. Subsequent recurrence was found in 4 of these patients but in none of 5 patients with FISH-negative results. Multiprobe FISH markedly improves the sensitivity and specificity of cytology for the detection of bladder cancer in urine specimens. Diagnosis of primary and recurrent bladder cancer is one of the most difficult problems in urology and cytology. Bladder cancer is a chronic illness, and the patients need continuous surveillance for early detection of recurrence and progression. Noninvasive papillary urothelial tumors (pTa) recur in about 70% and progress in about 5% to invasive cancer. 1 The tumors with invasion limited to the lamina propria (stage pT1) pose the greatest clinical problem. Local progression to potentially life-threatening muscle-invasive cancer (pT2-4) occurs in 20% to 30% of these tumors after conservative surgical treatment. Cystoscopy has been the standard method for diagnostic evaluation of patients with symptoms of bladder cancer. Cystoscopies at regular intervals also are necessary to monitor patients for recurrence or progression of previously treated bladder cancer. Standard cytology has been regarded as an additional diagnostic tool to select patients for cystoscopic evaluation. However, the sensitivity of cytology in urinary specimens is limited, since most of the noninvasive cancers (stage pTa) are missed. 2-4 Therefore, cytology alone is too unreliable to serve as a basis for therapy decisions. Several attempts have been made to improve the detection of cancer cells in urinary samples by multiple urinary tumor markers or test assays (reviewed by Ross and Cohen 4 ). However, most of these markers are technically complicated and not sufficiently sensitive or specific to become an everyday tool to select patients for individual follow-up schemes or even to replace cystoscopy. The main problems are high false-positive rates owing to benign conditions and the lack of reproducibility of some tests if applied at different institutions. Fluorescence in situ hybridization (FISH) is a rapid and powerful technique to detect cytogenetic abnormalities in malignant cells independent of their functional status.