Clear cell papillary renal cell carcinoma: micro-RNA expression profiling and comparison with clear cell renal cell carcinoma and papillary renal cell carcinoma

Abstract

Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade renal neoplasm with morphological characteristics mimicking both clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC). However, despite some overlapping features, their morphological, immunohistochemical, and molecular profiles are distinct. Micro-RNAs (miRNAs) are small noncoding RNAs that play a crucial role in regulating gene expression and are involved in various biological processes, including cancer development. To better understand the biology of this tumor, we aimed to analyze the miRNA expression profile of a set of CCPRCC using microarray and quantitative reverse transcription-polymerase chain reaction. A total of 15 cases diagnosed as CCPRCC were used in this study. Among the most differentially expressed miRNA in CCPRCC, we found miR-210, miR-122, miR-34a, miR-21, miR-34b*, and miR-489 to be up-regulated, whereas miR-4284, miR-1202, miR-135a, miR-1973, and miR-204 were down-regulated compared with normal renal parenchyma. To identify consensus of differentially regulated miRNA between CCPRCC, CCRCC, and PRCC, we additionally determined differential miRNA expression using 2 publically available microarray data sets from the NCBI Gene Expression Omnibus database (GSE41282 and GSE3798). This comparison revealed that the miRNA expression profile of CCPRCC shows some overlapping characteristics between CCRCC and PRCC. Moreover, CCPRCC lacks dysregulation of important miRNAs typically associated with aggressive behavior. In summary, we describe the miRNA expression profile of a relatively infrequent type of renal cancer. Our results may help in understanding the molecular underpinning of this newly recognized entity.

Keywords: Clear cell papillary renal cell carcinoma; Micro-RNA; Profiling; Renal cancer.

Fig. 1

Histologic and immunohistochemical features of CCPRCC. A, Tumor cells showed typical nuclear arrangement away from the basement membrane. B, Small tubules and acini imparting a solid appearance admixed with delicate papillary structures. C, CK7 showed strong and diffuse positivity. D, CAIX showed the typical basal staining lacking the luminal aspect. E, AMACR resulted negative in all cases; normal distal tubules were positive. F, CD10 was negative or weakly positive. A, Original magnification HE, ×20; B, HE, ×10; C to F, ×10.

Fig. 2

Consensus among miRNA profiles associated with distinct renal carcinoma histotypes and stages. Lines above the 45° diagonal lines correspond to comparisons having more agreement than would be expected by chance. Lines in the white area of the graph have a probability of agreeing by chance of less than 1E-06. Genes were ranked by t-statistic as obtained from the linear model analysis. A, CAT curves for the following comparisons: miRNA up-regulated and down-regulated in clear cell papillary and clear cell tumors; miRNA up-regulated and down-regulated in papillary and clear cell papillary tumors. B, CAT curves for the following comparisons: miRNA up-regulated and down-regulated in clear cell papillary and in primary clear cell tumors; miRNA up-regulated and down-regulated in clear cell papillary and clear cells tumor metastasis.

Fig. 3

Technical and independent set validation of miR-122, miR-135a, and miR-204. A, Average fold changes of samples used for the microarray experiments (4) and qRT-PCR experiments (11). B, Relative expression on the 3 miRNAs in all 15 cases.