GDNF expression in Wilms tumor

Purpose: Wilms tumor or nephroblastoma is a developmental tumor of the kidn ey and one of the most frequent solid tumors in childhood. It derives from metanephrotic blastema and mimics nephrogenesis in a disorganized manner, o ffering an adequate model for study of human nephrogenesis. GDNF (glial cel l line derived neurotrophic factor), a potent proliferation and survival fa ctor of dopaminergic neurons, has recently been shown to have an early and major role in nephrogenesis. We studied the expression of GDNF in Wilms tum or. Materials and Methods: The study included 20 patients with nephroblastoma w hose age at surgery ranged from 2 months to 13 years. Expression of GDNF pr otein was analyzed by an immunohistochemical technique using anti-G;DNF ant ibody. Presence of GDNF-messenger (m)RNA and receptors GFR alpha1 and GFR a lpha2-mRNA was analyzed by reverse transcription polymerase chain reaction. Specimens were also studied to evaluate apoptosis, proliferation index and Bcl-2 expression. Results: GDNF expression was mainly found in the epithelial cells of the mo st differentiated tubes, GDNF and co-receptors mRNA were found in specimens and proliferative activity was found on the same tubes as GDNF expression. Bcl-2 was expressed strongly in epithelial cells, in an intermediate fashi on in the blastema and faintly in mesenchyma. Apoptosis was of low frequenc y in structures strongly expressing GDNF. Conclusions: We have shown that GDNF is expressed by nephroblastoma tissue of human kidneys. This expression is mainly in the differentiated epithelia l component of the nephroblastoma. We have also shown that tissue strongly expressing GDNF is positively proliferative and has less apoptotic activity . We speculate that the role of GDNF may not be limited to normal nephrogen esis but may interact with other factors in the process of proliferation an d apoptosis involved in nephroblastoma tumorigenesis.