Genetic alterations in urinary bladder carcinosarcoma: Evidence of a common clonal origin

The cellular origin of carcinosarcoma of the bladder is unknown. We address ed this issue by using microsatellite analysis for loss of heterozygosity ( LOH) in both the carcinomatous and sarcomatous components of 6 bladder tumo rs. We tested 40 microsatellite markers from 19 human chromosomes and compa red the genetic alterations between the two separately isolated components. The potential relevance of the E-cadherin pathway was also evaluated by im munohistochemistry. All 6 cases revealed identical LOH on chromosomal arms 9p, 9q, 8p, and 8q, corresponding to relatively early events in bladder car cinogenesis. Discordant losses between two alleles in the remaining chromos omes, associated with progression, were seen in all tumors with a trend tow ard a higher incidence in the more advanced tumors (N1M1 and N1Mx). E-cadhe rin was strongly expressed in the carcinomatous components (5 of 6), wherea s most of sarcomatous elements displayed absence of the protein product (4 of 6). These results indicate that both the carcinomatous and sarcomatous c omponents of carcinosarcoma are derived from a common stem cell. Downregula tion of E-cadherin may define one of the pathways responsible for conversio n of epithelial cells to the sarcomatous phenotype. Copyright (C) 2000 S. K arger AG, Basel.