Expression And Significance Of Phosphorylated-Stat3,Phosphorylated-Akt,CyclinD1 In Paget Disease

Objective:To understand the expression of p-Stat3,p-Akt and their downstream target gene cyclinDl protein in Paget disease and make a further exploration to study the influence of the Stat3 signal transduction pathway and Akt signal transduction pathway on the occurrence and development of Paget disease.Methods:Immunohistochemistry was adopted to detect the protein expression of p-Stat3,p-Akt and cyclinD1 in 21 cases of Paget disease, of which 12 cases were mammary Paget disease and 9 cases were extra mammary Paget disease,15 cases of syringoma and 10 cases of normal skin tissue specimen. Image analysis technology was introduced to measure and quantify the mean optical density of the positive expression of p-Stat3, p-Akt and cyclinD1, and after that, the correlation analysis of the expression of three proteins were conducted.Results:(1) In PD group, syringoma group and control group, the mean optical density of p-Stats3 expression were 0.354±0.039,0.172±0.034,0.174±0.025 respectively. The high expression of p-Stat3 in Paget showed a statistical significant difference (P<0.001)in Paget disease compared with syringoma and normal tissue. There was no statistical signficance difference in syringoma compared with normal tissue(P>0.05);The mean optical density of p-Akt expression in PD group,syringoma group and control group were 0.299±0.042,0.167±0.028,0.174±0.029 respectively. The high expression of p-Akt and showed a statistical significant difference (P<0.001)in Paget disease compared with syringoma and normal tissue. There was no statistical significance difference in syringoma compared with normal tissue(P>0.05); The mean optical density of cyclinD1 expression in PD group,syringoma group and control group were 0.299±0.042,0.167±0.028,0.174±0.029 respectively. The high expression of cyclinDl and showed a statistical significant difference (P<0.001) in Paget disease compared with syringoma and normal tissue. There was no statistical significance difference in syringoma compared with normal tissue (P>0.05).(2) The expression difference of the three proteins (p-Stat3,p-Akt and cyclinD1) in MPD and EMPD had no statistical significance difference (all P>0.05).(3)In Paget disease, the expression correlation between p-Stat3 and cyclinDl was positive(r=0.809, P＜0.05), p-Akt and cyclinDl was positive (r=0.776, P＜0.05), p-Stat3 and p-Akt was positive (r=0.776, P＜0.05).Conclusions:(1) The over-expression of p-Stat3,p-Akt and cyclinDl in Paget disease indicate that JAK/Stat3 and PI3K/Akt Signal transduction pathway activate in Paget disease and probably play a significant role in the process of Paget disease's occurrence and development. (2) The growth and proliferation of the tumor cells are enhanced by the over-expression of cyclinD1, which is induced by p-Stat3,p-Akt probably via JAK/Stat3 and PI3K/Akt signal transduction pathway.