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

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.

Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer

“…38 Genetic studies suggest that the epithelial and sarcomatoid elements share a common monoclonal cell origin. 39,40 The reported incidence has ranged from 0.2% to 4.3%. 41 This suggestion has been confirmed in an analysis of the Surveillance, Epidemiology and End Results (SEER) database.…”

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas

“…The primers used for TP53 sequencing have been previously described [38,39]. 50 ng tumour DNA was amplified and sequencing reactions were carried out using the DNA Sequencing Kit BigDye Terminator v 1.1 Cycle Sequencing Ready Reaction Mix (Applied Biosystems, Warrington, UK), as previously described [40].…”

Carcinosarcoma of the upper urinary tract with an aggressive angiosarcoma component

“…18,20 In addition, identical TP53 mutations and concordant p53 expression patterns were detected in both the epithelial and sarcomatoid tumor components in 5 of 17 patients with CS of the urinary bladder. 17 In our case, however, TP53 sequencing of exons 5, 7 and 8 in the urothelial carcinoma and in the angiosarcoma tissue failed to detect TP53 mutations, and immunostaining for p53 was positive in a very low percentage of cells in both components.…”

“…4,16 Findings from several studies lend support to the divergence hypothesis. [17][18][19][20] For example, studies examining loss of heterozygosity in patients with CS of the bladder found identical patterns between the epithelial and sarcomatoid components of the tumors, [18][19][20] although identical patterns were more frequent in genetic alterations related to early events in bladder carcinogenesis rather than those associated with later events. 18,20 In addition, identical TP53 mutations and concordant p53 expression patterns were detected in both the epithelial and sarcomatoid tumor components in 5 of 17 patients with CS of the urinary bladder.…”