Expression of phosphorylated Stat3, cyclin D1 and Bcl-xL in extramammary Paget disease

Abstract

Background Stat3 (Signal transducer and activator of transcription‐3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl‐xL) and cell cycle regulators (cyclin D₁). The expression of Stat3, Bcl‐xL and cyclin D₁ protein has not been investigated in extramammary Paget disease (EMPD). Objectives To study the expression of phosphorylated Stat3 (p‐Stat3), Bcl‐xL and cyclin D₁ protein in EMPD and to evaluate the relationships among them. Methods Thirty‐six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p‐Stat3, cyclin D₁ and Bcl‐xL. Results Thirty‐five of 36 specimens were clearly positive for p‐Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D₁ and Bcl‐xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p‐Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p‐Stat3 staining. There were significant correlations between p‐Stat3 and cyclin D₁ expression and between p‐Stat3 and Bcl‐xL expression. Conclusions Our study shows that the expression of p‐Stat3, cyclin D₁ and Bcl‐xL may play a pivotal role in the pathogenesis of EMPD.