title: Molecular classification of adult renal epithelial neoplasms using microRNA expression and virtual karyotyping.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Methodist Hospital and The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Powers
authors.forename: Karla
authors.initials: K
authors.lastname: Alvarez
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Federico A
authors.initials: FA
authors.lastname: Monzon
mesh_terms: D006801:Humans; D007621:Karyotyping / Q000379:methods; D007680:Kidney Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods*; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification / Q000235:genetics / Q000473:pathology*
chemical_list: D035683:MicroRNAs