Search

Conventional urine cytology has a poor prognostic performance for detecting bladder cancer, particularly for low-grade tumors. Fluorescence in situ hybridization (FISH) for chromosomes altered in bladder cancer and testing for antigens selectively expressed in tumors are promising alternatives. This study investigated the use of FISH for detecting aneuploidy of chromosomes 3, 7, 17, and 9p21 and reverse transcriptase PCR (RT-PCR) for the expression of melanoma associated antigen (MAGE) genes for the diagnosis of bladder cancer in voided urine specimens. The two techniques were compared with cystoscopic bladder biopsy results in 47 patients with urothelial cancer and 15 patients with benign prostatic hyperplasia. FISH detected cancer in 42 of 47 patients (89.4%). This was significantly higher than the detection rate 30 of 47 patients (64.3%) by MAGE RT-PCR (P < 0.001). The sensitivity of FISH increased with histologic grade and stage of the tumors, correctly identifying 77.8% of pTa and pTis, 94.1% of pT1, and 100% of Pt2-4 tumors. MAGE, however, showed a decreased sensitivity in high grade advanced tumors; it was positive in 66.7% of pTa and pTis, 70.6% of pT1, and 50% of Pt2-4 tumors. Together, the tests correctly identified urothelial cancer in 46 of 47 patients (97.9%). Combined FISH and MAGE RT-PCR testing may offer a promising alternative to conventional urine cytology in screening high-risk populations and in monitoring bladder cancer patients for recurrent tumor.

Identification of molecular alterations in biological fluids has been proposed as a powerful tool for cancer diagnosis. The purpose of this study was to identify cells that carry chromosomal alterations indicative of malignancy-specifically, gains in the loci 5p15.2 (D5S23, D5S721), 6p11 approximately q11, 7p12 (EGFR), and 8q24.12 approximately q24.13 (MYC)-for the detection of lung cancer using induced sputum. The overall sensitivity of the multicolor fluorescence in situ hybridization (FISH) assay from 52 lung cancer patients was 71% and the specificity was 100% (15 of 15). The most frequently detected gains were at 7p12 (EGFR) in 17 of 24 completely resectable early-stage (II+IIIA) non-small cell lung cancers (NSCLC) (71%). There was a statistically significant increase in the proportion of cases with gains of EGFR in squamous cell carcinomas (SCC), compared with adenocarcinomas (AC) (82 vs. 43%, respectively; P = 0.017), and a higher average EGFR gene copy number in the SCCs than in the ACs (5.04 vs. 3.78, respectively; P = 0.013) in 41 NSCLCs. Conversely, a gain at the 6p11 approximately q11 and 8q24.12 approximately q24.13 (MYC) regions appears to have a higher frequency of gain in the ACs (71 and 86%, respectively) than in the SCCs (48 and 56%, respectively). The results of this study showed the potential utility of the LAVysion FISH assay for the detection of lung cancer by a noninvasive technique based on the analysis of genetic alterations of induced sputum. Defining abnormalities in sputum specimens as FISH aneusomy may be a possible diagnostic method for the early detection of lung cancer in screening of high-risk populations and monitoring for recurrence.