TP53 mutational analysis supports monoclonal origin of biphasic sarcomatoid urothelial carcinoma (carcinosarcoma) of the urinary bladder

Andrew B. Armstrong, Mingsheng Wang, John N. Eble, Gregory T. MacLennan, Rodolfo Montironi, Puay Hoon Tan, Antonio Lopez-Beltran, Shaobo Zhang, Lee Ann Baldridge, Helena Spartz, Liang Cheng

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Sarcomatoid urothelial carcinoma of the urinary bladder is an uncommon neoplasm with biphasic morphology exhibiting both epithelial and sarcomatoid components. Whether this tumor arises from a single cancer stem cell with subsequent differentiation or represents collision of the progeny of two separate cancer stem cells is a matter of controversy. To clarify its clonal origin, we analyzed the TP53 mutation status of a series of 17 sarcomatoid urothelial carcinomas using single-strand conformation polymorphism, DNA sequencing and p53 immunohistochemistry. Sarcomatoid and epithelial tumor components were separately microdissected using laser capture microdissection. Five out of the 17 sarcomatoid urothelial carcinomas contained TP53 point mutations in exons 5 and 8. In all five cases, the TP53 point mutations were identical in both the epithelial and sarcomatoid components. The sarcomatoid and epithelial tumor components in all 17 cases showed concordant p53 expression patterns. Our results suggest that despite their conspicuous divergence at the phenotypic level, the sarcomatoid and carcinomatoid elements of this uncommon tumor share a common clonal origin.

Original languageEnglish (US)
Pages (from-to)113-118
Number of pages6
JournalModern Pathology
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Cancer stem cells
  • Clonality
  • Molecular genetics
  • Sarcomatoid urothelial carcinoma
  • Tumorigenesis
  • Urinary bladder

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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