Glial cell line-derived neurotrophic factor and synaptophysin expression in pelviureteral junction obstruction.

Objectives: To examine the expression of neuronal markers in congenital pelviureteral junction (PUJ) obstruction as a causative factor. The findings from some investigations have suggested that defective neuronal innervation may play an important role in the pathogenesis of PUJ obstruction.

Methods: Using specific antibodies, we studied the neuronal markers of specimens from 12 cases of PUJ obstruction and 10 normal PUJs by immunohistochemistry using glial cell line-derived neurotrophic factor (GDNF), synaptophysin, S-100, and neurofilament.

Results: In the PUJ obstruction specimens, staining with hematoxylin-eosin and Masson's trichrome revealed muscular hypertrophy and an increase in collagen tissue and fibrosis in the lamina propria and tunica muscularis. The most striking finding on immunohistochemistry was the marked nuclear staining of cells with synaptophysin in all layers of the PUJ obstruction specimens that was totally absent in the normal PUJ specimens. In addition, significantly less intense staining for GDNF was found in the PUJ obstruction specimens compared with the normal PUJ specimens. The underexpression of GDNF in PUJ obstruction specimens was localized in the muscular layer especially. Immunohistochemical staining for S-100 and neurofilament showed no differences in the expression level of these neuronal markers in normal and PUJ obstruction specimens.

Conclusions: Because GDNF is a survival factor for central and peripheral neurons, defective expression of GDNF could play an important role in the defective neuronal innervation of PUJ obstruction. Intense nuclear expression of synaptophysin in all layers of obstructed PUJ specimens suggested that obstructed PUJs have a serious structural abnormality.