Molecular-genetic alterations as criteria in differential diagnostics of rare renal tumors

Apolihin O.I., Mihaylenko D.S., Mihal'chenko A.E., Zaletaev D.V., Efremov G.D., Sivkov A.V.

Renal cancer is a heterogeneous group of tumors, the most common of which is the clear cell carcinoma, less common papillary and chromophobe carcinomas. Pathological examination faces difficulties in the differential diagnosis of malignant chromophobe carcinoma and benign oncocytomas, and between types I and II papillary renal carcinoma. However, the precise verification of these types of tumors is required for an adequate prognosis and treatment planning. We have provided search for STR-markers and a complex molecular genetic analysis of chromosome 1, 2, 6, 10, 13q, 21q and 17 in four chromophobe carcinomas and three oncocytomas, and analysis of the MET gene mutations in 13 papillary carcinomas to develop criteria for differential diagnosis of rare tumors of the kidney. It was demonstrated that allelic imbalance and/or microsatellite instability in two or more from the 12 selected loci are characteristic for chromophobe carcinomas and missing in oncocytomas (p = 0.029). Next, we have performed development of criteria for the differential diagnosis of chromophobe carcinomas and oncocytomas by the supervised classification analysis, based on a logistic regression model with regularization. Accuracy on the training set was more than 90%, which allows us to clearly determine the pattern of alterations in 10 STR-markers typical for chromophobe carcinoma. Somatic mutations in the MET gene, in contrast, cannot be considered as diagnostic markers of papillary carcinoma type I due to the low frequency. Thus, we have provided a method for differential diagnosis of chromophobe renal cell carcinoma and oncocytoma by molecular genetic analysis of the primary tumor.

The reported study was partially supported by RFBR, research project No. 12-04-31005 мол_a.

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