GDNF expression in Wilms tumor.
OBJECTIVE
Wilms tumor or nephroblastoma is a developmental tumor of the kidney and one of the most frequent solid tumors in childhood. It derives from metanephrotic blastema and mimics nephrogenesis in a disorganized manner, offering an adequate model for study of human nephrogenesis. GDNF (glial cell line derived neurotrophic factor), a potent proliferation and survival factor of dopaminergic neurons, has recently been shown to have an early and major role in nephrogenesis. We studied the expression of GDNF in Wilms tumor.


METHODS
The study included 20 patients with nephroblastoma whose age at surgery ranged from 2 months to 13 years. Expression of GDNF protein was analyzed by an immunohistochemical technique using anti-GDNF antibody. Presence of GDNF-messenger (m)RNA and receptors GFRalpha1 and GFRalpha2-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 most 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 fashion in the blastema and faintly in mesenchyma. Apoptosis was of low frequency 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 epithelial 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 nephrogenesis but may interact with other factors in the process of proliferation and apoptosis involved in nephroblastoma tumorigenesis.
Séguier-Lipszyc
E
E
Department of Pediatric Surgery, Hôpital Robert Debré, Paris, France.
El-Ghoneimi
A
A
Brinon
C
C
Florentin
A
A
Simonneau
M
M
Aigrain
Y
Y
Peuchmaur
M
M
D000293:Adolescent; D034961:Antigens, Nuclear; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000378:metabolism*
D034961:Antigens, Nuclear; C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2