Lin Nengxing, Uchi Hiroshi, Moroi Yoichi, Fukiwake Noriko, Dainichi Teruki, Takeuchi Satoshi, Takahara Masakazu, Tu Yating, Furue Masutaka, Urabe Kazunori
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan.
J Dermatol Sci. 2007 Mar;45(3):187-92. doi: 10.1016/j.jdermsci.2006.12.003. Epub 2007 Jan 5.
The p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappaB (NF-kappaB)/cyclin D1 signaling pathway has recently been shown to play an important part in the pathogenesis of many human tumors. However, the role of this signal transduction pathway in extramammary Paget's disease (EMPD) remains unknown.
This study was designed to investigate the expression of phosphorylated p38 MAP kinasealpha (p-p38 MAPKalpha), phosphorylated NF-kappa B p65 (p-NF-kappaB p65) and cyclin D1 proteins in EMPD and to evaluate the relationship among them.
Thirty-five tissue samples from 30 primary EMPD cases were analyzed by immunohistochemical staining in formalin-fixed, paraffin-embedded tissue sections for p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1.
Among the 35 specimens of EMPD, p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1 were expressed in 30, 28 and 27, respectively. Moreover, in five metastatic lymph node specimens, all were positive for p-p38 MAPKalpha and p-NF-kappaB p65, four were positive for cyclin D1. There were significant correlations between expression of p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 in EMPD.
This study provides evidence that p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 was overexpressed in EMPD, suggesting that the p38 MAPK/NF-kappaB/cyclin D1 signaling pathway might participate in the oncogenesis of EMPD.
p38丝裂原活化蛋白激酶（MAPK）/核因子κB（NF-κB）/细胞周期蛋白D1信号通路最近被证明在许多人类肿瘤的发病机制中起重要作用。然而，该信号转导通路在乳腺外佩吉特病（EMPD）中的作用仍不清楚。
本研究旨在探讨磷酸化p38丝裂原活化蛋白激酶α（p-p38 MAPKα）、磷酸化NF-κB p65（p-NF-κB p65）和细胞周期蛋白D1蛋白在EMPD中的表达，并评估它们之间的关系。
对30例原发性EMPD病例的35个组织样本进行免疫组织化学染色分析，检测福尔马林固定、石蜡包埋组织切片中的p-p38 MAPKα、p-NF-κB p65和细胞周期蛋白D1。
在35个EMPD标本中，p-p38 MAPKα、p-NF-κB p65和细胞周期蛋白D1分别在30个、28个和27个标本中表达。此外，在5个转移淋巴结标本中，所有标本的p-p38 MAPKα和p-NF-κB p65均为阳性，4个标本的细胞周期蛋白D1为阳性。EMPD中p-p38 MAPKα、p-NF-κB p65和细胞周期蛋白D1的表达之间存在显著相关性。
本研究提供证据表明，p-p38 MAPKα、p-NF-κB p65和细胞周期蛋白D1在EMPD中过表达，提示p38 MAPK/NF-κB/细胞周期蛋白D1信号通路可能参与EMPD的肿瘤发生。
