MicroRNA (miRNA) Profiling of Clear Cell Papillary Renal Cell Carcinoma (CCP)
Pawel A Mroz, Bing Zhu, Xiaoqi Lin, Ximing J Yang, Stephen M Rohan. Northwestern University, Chicago, IL
Background: CCP is a recently described novel subtype of renal cell carcinoma (RCC) that differs from clear cell RCC (CRCC) and papillary RCC (PRCC) at the morphological, immunohistochemical, and molecular levels. Recent data has suggested that CCP has a more indolent behavior than CRCC and PRCC and, thus, differentiating these tumor types may be clinically relevant. Prior studies have shown that CCP lacks the characteristic chromosomal changes observed in CRCC and PRCC. However, no specific recurrent molecular changes have been described in CCP to date. To evaluate whether CCP differs genetically from non-neoplastic kidney (NK) and other RCC subtypes we initiated a pilot project that aims to evaluate the miRNA expression profiles in a series of CCPs compared to NK, CRCC and PRCC.
Design: We utilized formalin fixed paraffin embedded tissue from 10 CCP, 10 CRCC, 5 PRCC, and 2 CCRCC arising in patients with germline Von Hippel Lindau gene mutations (CRCC-V) along with matched NK samples and evaluated miRNA profiles with whole transciptome miRNA arrays (WTAv16.0, HTG molecular). An additional 8 un-matched NK samples were evaluated using the same arrays. Statistical analyses and hierarchical clustering (Partek Genomic Suite) were performed to identify miRNAs differentially expressed in CCP when compared to NK and other RCC subtypes. Only miRNAs showing ≥ 2-fold change with p-values of < 0.05 were considered to be significant.
Results: Compared to NK, CCP exhibited significantly decreased expression of 37 miRNAs and overexpression of 2 miRNA (miR-210, miR-489). In contrast CRCC-V, CRCC, and PRCC showed relative overexpression of 13, 21 and 67 miRNAs respectively when compared to NK. Further analysis revealed that CCP significantly underexpressed 4, 39, and 99 miRNAs when compared to CRCC-V, CRCC and PRCC respectively. Four miRNAs (miR-489, miR-143, miR-145 and miR-199a-5p) were overexpressed in CCP relative to PRCC. No miRNAs were significantly overexpressed in CCP relative to CRCC or CRCC-V.
Conclusions: Relative to NK and other RCC subtypes, CCP shows globally decreased expression of miRNAs. miR-489 is significantly up-regulated in CCP relative to NK and PRCC. Our results suggest that the miRNA profile of CCP is distinct from that of NK, CRCC-V, CRCC, and PRCC. Further validation of these findings using additional methods, such as qPCR, and a larger number of specimens is required to characterize and confirm the observed changes.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 145, Monday Morning