Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays.

Biocruces Bizkaia Health Research Institute Barakaldo Spain

Biogipuzkoa Health Research Institute Oncology Area Molecular Oncology Group San Sebastian Spain

Biogipuzkoa Health Research Institute Oncology Area Molecular Oncology Group San Sebastian Spain; IKERBASQUE Basque Foundation for Science Bilbao Spain; Sino Swiss Institute of Advanced Technology University of Shanghai Shanghai China; Radcliffe Department of Medicine University of Oxford Oxford UK

Department of Pathology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Pathology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic; Bioptical Laboratory Ltd Pilsen Czech Republic

Department of Pathology Maria Victoria Hospital ASL Città di Torino Turin Italy

Department of Pathology National Institute of Cancer Mexico City Mexico

Department of Pathology San Giovanni Bosco Hospital ASL Città di Torino Turin Italy; Department of Sciences of Public Health and Pediatrics University of Turin Italy

Department of Pathology Stradin's University Riga Latvia

References provided by Crossref.org

Acceptance of emerging renal oncocytic neoplasms: a survey of urologic pathologists