Expression profiling of renal epithelial neoplasms - A method for tumor classification and discovery of diagnostic molecular markers

The expression patterns of 7075 genes were analyzed in four conventional (c lear cell) renal cell carcinomas (RCC), one chromophobe RCC, and two oncocy tomas using cDNA microarrays. Expression profiles were compared among tumor s using various clustering algorithms, thereby separating the tumors into t wo categories consistent with corresponding histopathological diagnoses. Sp ecifically, conventional RCCs were distinguished from chromophobe RCC/oncoy tomas based on large-scale gene expression patterns. Chromophobe RCC/oncocy tomas displayed similar expression profiles, including genes involved with oxidative phosphorylation and genes expressed normally by distal nephron, c onsistent with the mitochondrion-rich morphology of these tumors and the th eory that both lesions are related histogenetically to distal nephron epith elium. Conventional RCCs underexpressed mitochondrial and distal nephron ge nes, and were further distinguished from chromophobe RCC/oncocytomas by ove rexpression of vimentin and class II major histocompatibility complex-relat ed molecules. Novel, tumor-specific expression of four genes-vimentin, clas s II major histocompatibility complex-associated invariant chain (CD74), pa rvalbumin, and galectin-3-was confirmed in an independent tumor series by i mmunohistochemistry, Vimentin was a sensitive, specific marker for conventi onal RCCs, and parvalbumin was detected primarily in chromophobe RCC/oncocy tomas. In conclusion, histopathological subtypes of renal epithelial neopla sia were characterized by distinct patterns of gene expression, Expression patterns were useful for identifying novel molecular markers with potential diagnostic utility.