Loss of heterozygosity at 1p, 8p, 10p, 13q, and 17p in advanced urothelialcancer and lack of relation to chemotherapy response and outcome

Studies of urothelial tumors have identified structural abnormalities in a number of chromosomes. This study aimed to identify specific genetic change s of patients with advanced urothelial cancers, and relate these changes to increased chemotherapy sensitivity or good prognosis. We screened 56 muscl e-invasive bladder cancer tumors for loss of heterozygosity (LOH) at chromo some 1p, 8p, 10p, 13q, and 17p with PCR using 6 microsatellite markers. All patients had recurrent locally advanced or metastatic disease. DNA was ext racted after microdissection of the primary tumor and normal tissue from pa raffin-embedded specimens. The PCR products were electrophoresed in an ABI Prism 377 DNA sequencer and the alleles from tumor DNA and normal tissue DN A were analyzed using the GeneScan program. The LOH findings were correlate d with response to chemotherapy and survival. Allelic loss of specific mark ers was present in 26-50% of the informative tumors. The most frequent LOH was observed at 17p, supporting the notion that this region may contain gen es of importance to urothelial cancer progression. The overall rate of resp onse to chemotherapy was 48%, and ranged from 40% to 56% according to speci fic LOH changes. The median survival of all patients from start of chemothe rapy was 5.8 months and ranged from 5.3 to 7.9 months for patients with spe cific LOH changes. Response and survival of patients with no lost markers w as the same size, compared to patients with one, two, or more lost markers. Specific genetic changes were detected in a significant number of tumors f rom patients with advanced urothelial cancer. These changes were not predic tive of response to chemotherapy or of the duration of survival. (C) 2000 E lsevier Science Inc. All rights reserved.