Histogenesis of sarcomatoid urothelial carcinoma of the urinary bladder: Evidence for a common clonal origin with divergent differentiation

M. T. Sung, M. Wang, G. T. MacLennan, J. N. Eble, P. H. Tan, A. Lopez-Beltran, R. Montironi, J. J. Harris, M. Kuhar, L. Cheng

Research output: Contribution to journalArticle

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Abstract

The histogenesis of sarcomatoid urothelial carcinoma, a rare neoplasm with bidirectional epithelial and mesenchymal differentiation, has been a matter of controversy. To clarify its origin, we analysed the status of X-chromosome inactivation in sarcomatoid urothelial carcinomas from 10 female patients and examined losses of heterozygosity (LOH) in these specimens and in additional 20 tumours from nude patients. Six polymorphic microsatellite markers where genetic alterations occur frequently in early or advanced stages of urothelial carcinomas, including D3S3050, D8S261, IFNA, D9S177, D11S569 and TP53, were investigated in the current study. The identical pattern of non-random X-chromosome inactivation in both carcinomatous and sarcomatous components was identified in five of eight informative female patients, and the remaining three informative cases showed a random, but concordant, pattern of X-chromosome inactivation. The concordant X-chromosome inactivation results in all eight informative cases support the concept of a monoclonal origin of both components of this biphasic neoplasm. Among the tumours demonstrating loss of heterozygosity, high incidences of an identical pattern of allelic loss between carcinomatous and sarcomatous components were identified in genetic alterations associated with early carcinogenesis: 86% at D8S261, 78% at D11S569, 75% at D9S177 and 57% at IFNA. In contrast, concordant LOH patterns were less frequently observed for microsatellites related to advanced carcinogenesis: only 40% at D3S3050 and 40% at TP53. The significant overlap of loss of heterozygosity supports a monoclonal cell origin and suggests that clonal divergence may occur during tumour progression and differentiation. Divergent patterns of discordant allefic loss of microsateltite markers imply that heterogeneous pathogenetic pathways may exist in the evolution of this enigmatic neoplasm.

Original languageEnglish (US)
Pages (from-to)420-430
Number of pages11
JournalJournal of Pathology
Volume211
Issue number4
DOIs
StatePublished - Mar 1 2007

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Urinary Bladder
Loss of Heterozygosity
Carcinoma
X Chromosome Inactivation
Neoplasms
Microsatellite Repeats
Carcinogenesis
Incidence

Keywords

  • Carcinosarcoma
  • Clonality
  • Loss of heterozygosity
  • Neoplasia
  • Sarcomatoid
  • Urinary bladder
  • Urothelial carcinoma
  • X-chromosome inactivation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Histogenesis of sarcomatoid urothelial carcinoma of the urinary bladder : Evidence for a common clonal origin with divergent differentiation. / Sung, M. T.; Wang, M.; MacLennan, G. T.; Eble, J. N.; Tan, P. H.; Lopez-Beltran, A.; Montironi, R.; Harris, J. J.; Kuhar, M.; Cheng, L.

In: Journal of Pathology, Vol. 211, No. 4, 01.03.2007, p. 420-430.

Research output: Contribution to journalArticle

Sung, M. T. ; Wang, M. ; MacLennan, G. T. ; Eble, J. N. ; Tan, P. H. ; Lopez-Beltran, A. ; Montironi, R. ; Harris, J. J. ; Kuhar, M. ; Cheng, L. / Histogenesis of sarcomatoid urothelial carcinoma of the urinary bladder : Evidence for a common clonal origin with divergent differentiation. In: Journal of Pathology. 2007 ; Vol. 211, No. 4. pp. 420-430.
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