Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget's disease.
BACKGROUND
Activating transcription factor 2 (ATF2) and signal transducer and activator of transcription 3 (STAT3) play important roles in the pathogenesis of various tumors, but ATF2 expression/activation and the relationship with STAT3 activation have not yet been investigated in extramammary Paget's disease (EMPD).


OBJECTIVE
To investigate potential contributions of ATF2 and STAT3 pathways to the pathogenesis of EMPD.


METHODS
Paraffin-embedded 45 EMPD specimens (43 primary EMPD and 2 nodal metastases) were subjected to immunohistochemical staining for ATF2, phosphorylated (p)-ATF2 and p-STAT3.


RESULTS
P-ATF2 expression in advanced EMPD, non-invasive EMPD and normal skin (NS) controls were 97.9 +/- 1.8%, 82.0 +/- 23.4% and 45.8 +/- 3.2%, respectively, and p-STAT3 expression in advanced EMPD, non-invasive EMPD and NS were 97.0 +/- 2.9%, 83.2 +/- 23.3% and 50.1 +/- 6.7%, respectively. P-ATF2 and p-STAT3 expressions in EMPD were significantly higher than those in NS, indicating a possible contribution of these pathways to the tumor development. P-ATF2 and p-STAT3 expressions in advanced EMPD were significantly higher than those in non-invasive EMPD, possibly indicating that these pathways might also contribute to the tumor invasion and/or metastasis. We also found an exceptionally high positive correlation between p-ATF2 and p-STAT3 expressions in EMPD.


CONCLUSIONS
P-ATF2 and p-STAT3 are concordantly overexpressed in EMPD and their expressions may possibly be associated with the tumor stage.
Chen
Si-Yuan
SY
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takeuchi
Satoshi
S
Moroi
Yoichi
Y
Hayashida
Sayaka
S
Kido
Makiko
M
Tomoeda
Hiroto
H
Uenotsuchi
Takeshi
T
Tu
Ya-Ting
YT
Furue
Masutaka
M
Urabe
Kazunori
K
D051698:Activating Transcription Factor 2 / Q000096:biosynthesis*; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D015854:Up-Regulation
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human