title: 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.
authors.affiliation: Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Armstrong
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Baldridge
authors.forename: Helena
authors.initials: H
authors.lastname: Spartz
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002296:Carcinosarcoma / Q000235:genetics*; D019070:Cell Lineage; D002999:Clone Cells; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53