Differential expression of the multidrug resistance-related protein MRP1 in the histological compartments of nephroblastomas

Nephroblastomas (Wilms' tumors) arc curable with survival rates above 80%. Some tumors, however, fail to respond to therapy and those patients have a poor prognosis. In a search for prognostic markers, we investigated the expression of the multidrug resistance-related protein 1 (MRP1) in 32 nephroblastomas by means of immunohistochemistry. The immunohistochemical results were validated with a real-time RT-PCR technique. MRP1 expression was heterogeneous and predominately found in the blastemal and epithelial compartments compared to the stromal elements of nephroblastomas. We found significant relationships of MRP1 expression to survival of patients and to expression of p53, HSP70, and LRP/MVP. The relationship between MRP1 and p53 expression is a clue that the transcriptional control of MRP1 by p53 reported for other tumor types may also take place in nephroblastomas. The correlation of MRP1 to other drug resistance genes, e.g. HSP70 and LRP/MVP in nephroblastomas indicates that the co-expression of different drug resistance genes may be under a common regulation of still unknown transcription factors.