Accurate Molecular Classification of Kidney Cancer Subtypes Using MicroRNA Signature

Renal cell carcinoma (RCC) represents a spectrum of histologic subtypes that are morphologically and cytogenetically distinct. Distinguishing RCC subtypes is of clinical importance because they have different prognoses and subsequently different management plans. Attempts to distinguishing between the subtypes are usually made by morphologic assessment, which is often inconclusive and not always accurate. This can be caused by the complexity and mixed patterns of morphological features as well as simple observer variability in diagnosing subtypes among pathologists.

Researchers at the University of Toronto set out to identify microRNA signatures that can distinguish the different RCC subtypes accurately. Knowing the specific microRNA signature for each subtype provides the basis of a specific targeted therapy for the particular subtype by seeking the microRNAs.

MicroRNA microarray analysis was performed on fresh frozen tissues of three common RCC subtypes (clear cell, chromophobe, and papillary) and on oncocytoma (n=94). Results were validated on the original as well as on an independent set of tumours, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis with microRNA-specific primers.

From the microarray data, the researchers able to develop a classification system that can distinguish the different RCC subtypes using unique microRNA signatures in a maximum of four steps. The system has a sensitivity of 97% in distinguishing normal from RCC, 100% for clear cell RCC (ccRCC) subtype, 97% for papillary RCC (pRCC) subtype, and 100% accuracy in distinguishing oncocytoma from chromophobe RCC (chRCC) subtype. This system was cross-validated and showed an accuracy of about 90%. The oncogenesis of ccRCC is more closely related to pRCC, whereas chRCC is comparable with oncocytoma. They also developed a binary classification system that can distinguish between two individual subtypes.

Youssef YM, White N, Grigull J, Krizova A, Samy C, Mejia-Guerrera S, Evans A, Youse GM. (2011) Accurate Molecular Classification of Kidney Cancer Subtypes Using MicroRNA Signature. European Urology [Epub ahead of print]. [abstract]

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