Clear cell sarcoma of the kidney expresses insulinlike growth factor-II but not WT1 transcripts.

Two cases of clear cell sarcoma of the kidney (CCSK), five Wilms' tumors (WTs), and three fetal kidneys were studied by molecular hybridization to elucidate the histogenesis of CCSK. Northern blot and in situ hybridization demonstrated that all the CCSKs, WTs, and fetal kidneys contained abundant insulinlike growth factor-II (IGF-II) transcripts, whereas WTs and fetal kidneys--but not CCSKs--showed significant expression of WT1 gene, a candidate tumor suppressor gene implicated in the etiology of WTs. Comparative analysis of in situ hybridization of IGF-II and WT1 transcripts in CCSKs and fetal kidneys revealed that CCSK cells showed similar hybridization patterns to primitive metanephrogenic blastemal cells and early stromagenic cells. The data strongly suggest that CCSK is distinct from WT and may be derived from undifferentiated metanephrogenic blastemal cells with potential to differentiate into a stromal cell lineage. The result also suggests that this unique tumor should, more appropriately, be known as stromal--rather than clear--cell sarcoma of the kidney.