Paget病皮损中p-Stat3，p-Akt，cyclinD1蛋白表达及其相关分析

Expression of Phosphorylated-Stat3,Phosphorylated-Akt,cyclinD1 and Their Correlation in Paget Disease

目的探讨磷酸化细胞信号转导与转录活化因子3(p-Stat3)、磷酸化蛋白激酶B(p-Akt)、细胞周期蛋白D1(cyclinD1)在Paget病中的表达及意义。方法采用免疫组化法检测p-Stat3,p-Akt和cyclinD1在21例Paget病(包括乳房及乳房外)、15例汗管瘤和10例正常人皮肤组织中的表达水平,利用图像分析技术测量阳性细胞的平均光密度值,并对这3种蛋白的表达进行相关性分析。结果 Paget病中p-Stat3,p-Akt和cyclinD1的平均光密度值均明显高于汗管瘤和正常人皮肤组织,差异均有统计学意义(P均<0.001),而汗管瘤和正常皮肤组织比较差异无统计学意义(P>0.05);乳房Paget病与乳房外Paget病比较,p-Stat3,p-Akt和cyclinD1蛋白的表达差异均无统计学意义(P均>0.05);p-Stat3与cy-clinD1的表达,p-Akt与cyclinD1的表达及p-Stat3与p-Akt的表达均呈正相关(r=0.809,0.776,0.516,P均<0.05)。结论 Paget病中存在p-Stat3,p-Akt和cyclinD1的高表达,p-Stat3,p-Akt可能通过JAK/Stat3信号转导通路及PI3K/Akt信号转导通路诱导cyclinD1的过度表达,促使肿瘤细胞的生长及增殖。

Objective To explore the expressions of phosphorylated signal transducers and activators of transcription 3 （p-Star3）, phosphorylated protein kinase B （p-Akt）, cyclinD1 and their correlation in Paget disease. Methods The expression levels of p-Stat3, p-Akt and cyclinD1 in Paget disease （ n = 21 ）, including mammary Paget disease and extramammary Paget disease, were detected by the immunohistochemistry. In syringoma（ n = 15 ） and normal human skin tissues （n = 10） were also detected as control group. Image analysis technology was employed to measure and quantify the mean optical density of the positive protein expression of p- Stats, p-Akt and eyclinD1. The expressions and their relationship with the pathological factors were analyzed. Results The mean optical density of p-Stat3, p-Akt and cyclinD1 were obviously higher in Paget disease than those in Syringoma and normal human skin tissues. The high expressions of p-Stat3 ,p-Akt and cyclinD1 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 ）. There were no statistical significance difference （ P all 〉 0.05 ） among the expressions of p-Star3, p-Akt and cyclinD1 in MPD and EMPD . In Paget disease, positive correlation between expressions of p-Stat3 and cyclinD1, p-Akt and cyclinD1, p-Stat3 and p-Akt （ r = 0. 809, 0.776 and 0.776 respectively, P all 〈 0.05 ） were found. Conclusion There are high-expressions of p-Stat3, p-Akt and cyclinD1 in Paget disease. The growth and proliferation of the tumor cells was encouraged by the high-expression of cyclinD1, which was in- duced by p-Stat3 ,p-Akt probably via JAK/Stat3 and PI3K/Akt signal transduction pathway.