MicroRNAs as a Powerful Diagnostic Tools for the Differential Diagnosis of Kidney Tumors
E Fridman, Z Dotan, N Rosenfeld, Y Spector, A Faerman, I Barshack. Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; Rosetta Genomics Ltd, Rehovot, Israel
Background: Renal cell tumors are a group of tumors that differ both in morphologic appearance and biological behavior. In some cases, despite morphologic and immunohistochemical assessment, the pathological differential diagnosis can be difficult. Accurate diagnosis is essential for proper management of the patient. Additional diagnostic tools are therefore required. MicroRNAs are non-coding RNAs that regulate gene expression and display remarkable tissue specificity. Rosetta Genomics has developed technologies for extracting and profiling of microRNAs from FFPE samples. This technological platform was applied to differentiate between common types of kidney tumors.
Design: Two independent sets of kidney tumors FFPEs were collected and reviewed by a pathologist specializing in urological pathology. Histologically, renal cell tumors included: clear cell RCC, chromophobe RCC, papillary RCC (both subtypes) and oncocytoma and were classified using H&E stains. High-quality RNA was extracted using a protocol developed to preserve the fraction of microRNAs. Expression levels of microRNAs were measured on microarray and qRT-PCR platforms developed at Rosetta Genomics.
Results: Expression levels of over 800 microRNAs in a training set of over 70 kidney tumors identified differentially expressed microRNAs between the different histological types of renal cell tumors. We defined a simple algorithm for classification that uses a set of only 6 microRNAs to classify clear cell, chromophobe, papillary and oncocytoma tumors. The classifier was then tested on an independent validation set including the same histological types, and diagnosed correctly 91% of the tumors. Technical validation was performed using qRT-PCR showing a high correlation to the results obtained using microarrays.
Conclusions: Expression levels of certain microRNAs are highly specific to subtypes of kidney tumors. This evidence adds to the accumulating evidence on the specificity of microRNA expression in tissues, tumor types and developmental stages. A combination of 6 microRNAs can successfully answer specific differential diagnosis of morphologically similar renal cell tumors. The results we present provide a basis for the development of microRNA based diagnostic assay for renal oncology.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 104, Wednesday Afternoon