Molecular Classification of Renal Tumors by Gene Expression Profiling

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...

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Bibliographic Details
Published in:The Journal of molecular diagnostics : JMD 2005-05, Vol.7 (2), p.206-218
Main Authors: Schuetz, Audrey N., Yin-Goen, Qiqin, Amin, Mahul B., Moreno, Carlos S., Cohen, Cynthia, Hornsby, Christopher D., Yang, Wen Li, Petros, John A., Issa, Muta M., Pattaras, John G., Ogan, Kenneth, Marshall, Fray F., Young, Andrew N.
Format: Article
Language:English
Subjects:
Gene Expression Profiling
Genes, Neoplasm
Humans
Kidney Neoplasms - classification
Kidney Neoplasms - genetics
Kidney Neoplasms - pathology
Oligonucleotide Array Sequence Analysis
Regular
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Summary: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, α-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron markers (β-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.
ISSN:1525-1578
1943-7811
DOI:10.1016/S1525-1578(10)60547-8