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(American Journal of Pathology. 2001;158:1639-1651.)
© 2001 American Society for Investigative Pathology

Regular Articles

Expression Profiling of Renal Epithelial Neoplasms

A Method for Tumor Classification and Discovery of Diagnostic Molecular Markers

Andrew N. Young*§, Mahul B. Amin*{dagger}, Carlos S. Moreno{ddagger}, So Dug Lim*, Cynthia Cohen*, John A. Petros{dagger}§, Fray F. Marshall{dagger} and Andrew S. Neish*

From the Departments of Pathology and Laboratory Medicine,*
Urology,{dagger}
and Biochemistry,{ddagger}
Emory University School of Medicine, Atlanta; and the Atlanta VA Medical Center,§
Decatur, Georgia

The expression patterns of 7075 genes were analyzed in four conventional (clear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocytomas using cDNA microarrays. Expression profiles were compared among tumors using various clustering algorithms, thereby separating the tumors into two categories consistent with corresponding histopathological diagnoses. Specifically, conventional RCCs were distinguished from chromophobe RCC/oncocytomas based on large-scale gene expression patterns. Chromophobe RCC/oncocytomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, consistent with the mitochondrion-rich morphology of these tumors and the theory that both lesions are related histogenetically to distal nephron epithelium. Conventional RCCs underexpressed mitochondrial and distal nephron genes, and were further distinguished from chromophobe RCC/oncocytomas by overexpression of vimentin and class II major histocompatibility complex-related molecules. Novel, tumor-specific expression of four genes—vimentin, class II major histocompatibility complex-associated invariant chain (CD74), parvalbumin, and galectin-3—was confirmed in an independent tumor series by immunohistochemistry. Vimentin was a sensitive, specific marker for conventional RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocytomas. In conclusion, histopathological subtypes of renal epithelial neoplasia were characterized by distinct patterns of gene expression. Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.




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