title: Alterations in transcription clusters underlie development of bladder cancer along papillary and nonpapillary pathways.
abstract: Bladder cancer develops in the urothelial lining from intraurothelial preneoplasia via two pathways, papillary and nonpapillary, which correspond to nonaggressive and aggressive forms of the disease. Because these two forms of cancer may develop via distinct molecular events, we examined the gene expression patterns in the development of bladder cancer from preneoplasia along papillary and nonpapillary pathways. The expression profiles of 19 pairs of RNA samples from adjacent urothelium and tumors were analyzed using cDNA microarrays. For selected genes their expressions were verified on a cohort of 251 bladder cancer patients using tissue microarray and immunohistochemistry and were related to clinicopathological parameters including follow-up data. We identified alterations in seven gene clusters controlling proliferation, differentiation, and programmed cell death that were common for papillary and nonpapillary cancer. In contrast, genes controlling cellular and stromal interactions were altered in the nonpapillary cancer. The expression levels of only two genes from this group could be used to define an aggressive form of the disease. Tumors characterized by the low expression of e-cadherin and the high expression of DNA alpha-topoisomerase II had a high propensity for distant metastasis and were associated with poor survival.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jai-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Tomasz
authors.initials: T
authors.lastname: Tuziak
authors.forename: Limei
authors.initials: L
authors.lastname: Hu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: Jolanta
authors.initials: J
authors.lastname: Bondaruk
authors.forename: Misook
authors.initials: M
authors.lastname: Kim
authors.forename: Gregory
authors.initials: G
authors.lastname: Fuller
authors.forename: Colin
authors.initials: C
authors.lastname: Dinney
authors.forename: Herbert Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Keith
authors.initials: K
authors.lastname: Baggerly
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Bogdan
authors.initials: B
authors.lastname: Czerniak
mesh_terms: D018076:DNA, Complementary; D006801:Humans; D007150:Immunohistochemistry; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D018076:DNA, Complementary