Do the two components of sarcomatoid urothelial carcinoma share an origin?

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Sarcomatoid urothelial carcinoma is a rare neoplasm with both epithelial and mesenchymal differentiation, and its tissue origin has been controversial. To clarify its origin, researchers analysed X-chromosome inactivation in tumours from 10 female patients and examined loss of heterozygosity (LOH) in those specimens and 20 additional tumours from male patients. They investigated six polymorphic microsatellite markers where genetic alterations frequently occur in early or advanced urothelial carcinoma: D3S3050, D8S261, IFNA, D9S177, D11S569 and TP53.

Of eight informative female patients, five had identical non-random X-chromosome inactivation patterns in the carcinomatous and sarcomatous components, while the other three had random but matching patterns. The matching results in all eight informative cases support a monoclonal origin for both components of this two-component neoplasm.

Among tumours showing LOH, identical allelic-loss patterns between the two components were common at markers associated with early carcinogenesis: 86% at D8S261, 78% at D11S569, 75% at D9S177 and 57% at IFNA. Matching LOH patterns were less frequent at markers associated with advanced carcinogenesis: 40% at D3S3050 and 40% at TP53. The substantial overlap in LOH supports a monoclonal cell origin and suggests that clones may diverge during tumour progression and differentiation. Differing patterns of discordant allelic loss at the microsatellite markers imply that multiple pathogenetic pathways may exist as this neoplasm evolves.