Messenger RNA expression ratios among four genes predict subtypes of renal cell carcinoma and distinguish oncocytoma from carcinoma

Purpose Morphologic distinction among-clear cell papillary, and chromophobe types of renal cell carcinoma (RCC) can be difficult, as is the differential diagnosis between oncocytoma and RCC.Whether these renal tumors can be distiguished by their mRNA expression profile of a few selected genes was examined. Experimental Design: The expression of four genes in renal tumor was evaluated by quantitative reverse transcription-PCR: carbonic anhydrase IX (C,49); methylacyl-CoA racemase, (AMACR), (PVALB), and chloride channel kb (CLCNKB). Thirty-one fresh-frozen. and 3 formalin-fixed paraffin-embedded tumor specimens were analyzed. Results: CA9 expression was highest in clear cell carcinoma and lowest in chromophobe RCC and in oncocytoma, AMACR expression was highest in papillary, RCC, and CLCNKB was highest in chromophobe, RCC/oncocytoma. PVALB was highest in chromophobe RCC, variable in onco-cytoma, and low in clear cell and papillary types. Similar findings were observed in fresh-frozen and formalin-fixed specimens. The mRNA expression. ratios among,the se genes (i.e.,CA9/AMACR and AMACR/CLCNKB ratios) further accentuate gene expression differences among these,tumors, and a molecular diagnostic algorithm was established. This algorithm, accurately classified the 31 fresh-frozen tumors into 14 clear cell 5 papillary, 6 chromophobe, and 6 oncocytomas. In the formalin-fixed group,the molecular criteria accurately classified the cases into 15 clear cell, 16 papillary, and 32 in the chromophobe/oncocytoma group but could only separate some, but not all oncocytomas from chromophobe RCC. Conclusions:RNA expression ratios based on,the four-gene panel can accurately classify subtypes of RCC as Well as help distinguish some onco-cytomas from chromophobe RCC.