Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget's disease.

ABSTRACT

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. METHOD: 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.