Expression And Value Of P16,cyclinD1,pRb Protein Pathway In Neuroblastoma Development

Summary: Cell-cycle regulation depends on a fine balance between cyclin/cyclin-dependent kinase complexes and a family of kinase inhibitors that bind cyclin-cdk complexes and block their activity. Proliferation of cell is tightly controlled by a check-point in Gl phase known as the "restriction point" . Proteins involved in this control include the pl6/cyclinDl/pRb. If defective , the Gl checkpoint may lead to deregulated growth in specific cell, we considered the possibility that alerations of the Gl regulatory pathway in neuroblastoma, The abnormalities of p!6, pRb and cyclinDl proteins might be related to the development of neuroblastoma. We studied protein expression of p!6/cyclinDl/pRb cell cycle-regulatory proteins in neuroblastoma . To evaluate the significance of p!6, cyclinDl and pRb expression in neuroblastoma and the relationshipamong these three proteins.Methods: The immunohistochemical expression of P16/cyclinDl/pRb protein was studied in neuroblastoma (41 cases) and ganglioneuroma (39 caess)Results: The abnormality of p!6 expression was found in 39.0% (NB) and 74.4% (GN). the abnormality of pRb expression was found in 39.0% (NB) and 69.2%(GN). there was significant relationship between neuroblastoma and ganglioneuroma (p<0. 01). CyclinDl protein was highly expressed in neuroblastoma and ganglioneuroma. Overexpression of cyclinDl was found in 66. 7%(NB) and 85. 4%(GN). there was significant relationship between neuroblastoma and ganglioneuroma (p<0.05) . there was no significant relationship among these three proteins expression, there was no significant relationship between Rb pathway status and clinical factors.Conclusions : 1. the results of this study indicate that pRb and p!6 protein play an important role in the regulation of proliferation in neuroblastoma. 2. Overexpression of cyclinDl is a common molecular alteration that may occur in the early stage. cyclinDl protein may be responsible for growth deregulation in neuroblastoma. 3. overexpression of cyclinDl and/or the abnormality of p!6 or pRb expression may be involved in the pathogenesis of neuroblastoma. 4. The expression of the 3 proteins studied has no relation to tumor location, stages, age . It is also suggested that multiple genes abnormalities might be involved in the development of neuroblastoma.