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


OBJECTIVE
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.
Liu
H J
HJ
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan, and Department of Dermatology, Union Hospital, Hubei, China.
Moroi
Y
Y
Masuda
T
T
Yasumoto
S
S
Kokuba
H
H
Imafuku
S
S
Koga
T
T
Tetsuya
T
T
Tu
Y T
YT
Aburatani
H
H
Furue
M
M
Urabe
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D051020:bcl-X Protein; D019938:Cyclin D1