Detection of the ASPL-TFE3 and PRCC-TFE3 gene fusion in paraffin-embedded Xp11 translocation renal cell carcinomas

Xp11 translocation renal cell carcinomas (RCCs) are uncommon renal tumors, characterized by several different translocations involving the TFE3 gene. In these diseases, the TFE3 gene is fused by translocation to 1 of several other genes, including ASPL, PRCC, NONO (p54nrb), CLTC, PSF, LUC7L3, KHSRP, PARP14 and unknown genes on chromosomes 10. Tumors with different specific gene fusions may have slightly different clinical manifestations and morphologic features. In this study, we developed a FISH assay to detect the TFE3 gene rearrangement for the presence of the 2 most common fusion genes ASPL-TFE3 and PRCC-TFE3 inroutinely processed archival materials. 10 Xp11 translocation RCCs were detected TFE3 fusion genes. Cases 1-6 displayed fusion signals of ASPL-TFE3 and cases 7-10 demonstrated fusion signals of PRCC-TFE3. All cases contained a high percentage of cells displaying fusion signals for ASPL-TFE3 (mean, 45%; range, 35% to 60%) and for PRCC-TFE3 (mean, 45%; range, 35% to 60%). The sensitivity and specificity were both 100%. The interphase fluorescencein situ hybridization (FISH) assays should enable a more definitive identification of the ASPL-TFE3 and PRCC-TFE3 fusion gene in archival material and allow more meaningful clinicopathologic associations to be drawn.