Oncocytoma, chromophobe renal cell carcinoma (chRCC), and the eosinophilic 
variant of clear cell RCC (ccRCC) are morphologically similar tumors with 
significantly different clinical courses. These renal tumor subtypes show 
characteristic structural genetic changes; however, the mRNA expression patterns 
of oncocytoma and chRCC are strikingly similar. MicroRNAs (miRNA) are small RNA 
molecules that regulate the expression of many genes and have been shown to be 
useful for tumor classification and identification. The miRNA expression was 
analyzed from formalin-fixed paraffin-embedded tissue in 5 cases each of 
oncocytoma, ccRCC, papillary RCC, chRCC, and 4 normal kidney tissues using 
microarrays. Affymetrix single-nucleotide polymorphism arrays were used to 
detect chromosomal imbalances in each of the tumors. Eighteen miRNAs were 
significantly different among the 4 tumor types. The microRNA miR-21, a known 
oncogenic miRNA, was found to be upregulated in papillary and clear cell 
carcinomas. Four miRNAs could differentiate oncocytomas from chRCCs and the 3 
could differentiate papillary RCC from ccRCC, including miR-126, a known 
vasculogenic miRNA. Of the 18 differentially expressed miRNAs, only 2 correlated 
with copy number changes in the chromosomal region harboring these genes. One 
tumor, originally diagnosed as an oncocytoma by morphology, showed a virtual 
karyotype and miRNA expression pattern consistent with chromophobe carcinoma. 
Further investigation of the tumor showed vascular invasion. Our study suggests 
that miRNA expression can be used to differentiate the common subtypes of renal 
epithelial neoplasms but further validation is necessary. In addition, the lack 
of correlation between miRNA expression and virtual karyotype suggests a 
non-copy-number-related mechanism for miRNA gene expression regulation in renal 
neoplasia.