title: Molecular classification of renal tumors by gene expression profiling.
abstract: Renal tumor classification is important because histopathological subtypes are associated with distinct clinical behavior. However, diagnosis is difficult because tumor subtypes have overlapping microscopic characteristics. Therefore, ancillary methods are needed to optimize classification. We used oligonucleotide microarrays to analyze 31 adult renal tumors, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma. Expression profiles correlated with histopathology; unsupervised algorithms clustered 30 of 31 tumors according to appropriate diagnostic subtypes while supervised analyses identified significant, subtype-specific expression markers. Clear cell RCC overexpressed proximal nephron, angiogenic, and immune response genes, chromophobe RCC oncocytoma overexpressed distal nephron and oxidative phosphorylation genes, papillary RCC overexpressed serine protease inhibitors, and extracellular matrix products, and angiomyolipoma overexpressed muscle developmental, lipid biosynthetic, melanocytic, and distinct angiogenic factors. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry of formalin-fixed renal tumors confirmed overexpression of proximal nephron markers (megalin/low-density lipoprotein-related protein 2, alpha-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron markers (beta-defensin 1, claudin 7) in chromophobe RCC/oncocytoma. In summary, renal tumor subtypes were classified by distinct gene expression profiles, illustrating tumor pathobiology and translating into novel molecular bioassays using fixed tissue.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Decatur, GA 30033, USA.
authors.forename: Audrey N
authors.initials: AN
authors.lastname: Schuetz
authors.forename: Qiqin
authors.initials: Q
authors.lastname: Yin-Goen
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Moreno
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cohen
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hornsby
authors.forename: Wen Li
authors.initials: WL
authors.lastname: Yang
authors.forename: John A
authors.initials: JA
authors.lastname: Petros
authors.forename: Muta M
authors.initials: MM
authors.lastname: Issa
authors.forename: John G
authors.initials: JG
authors.lastname: Pattaras
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ogan
authors.forename: Fray F
authors.initials: FF
authors.lastname: Marshall
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Young
mesh_terms: D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D007680:Kidney Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis