Androgen receptor, androgen-producing enzymes and their transcription factors in extramammary Paget disease

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• 作者：Abdullah Azmahani ; MSc^a ; ^b ; Yasuhiro Nakamura ; MD ; PhD^a ; ^{yasu-naka@patholo2.med.tohoku.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yohei Ozawa ; MD ; PhD^a ; ^c ; Keely M. McNamara ; PhD^a ; Taku Fujimura ; MD ; PhD^d ; Takahiro Haga ; MD^d ; Akira Hashimoto ; MD^d ; Setsuya Aiba ; MD ; PhD^d ; Hironobu Sasano ; MD ; PhD^a
• 关键词：EMPD ; extramammary Paget disease ; 17尾-HSD5 ; 17尾-hydroxysteroid dehydrogenase type 5 ; 5伪-red1 ; 5伪-reductase type 1 ; 5伪-red2 ; 5伪-reductase type 2 ; AR ; androgen receptor ; ER ; estrogen receptor ; CK19 ; cytokeratin 19 ; FOXP1 ; forkhead box protein P1
• 刊名：Human Pathology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：46
• 期：11
• 页码：1662-1669
• 全文大小：1156 K

文摘

Extramammary Paget disease (EMPD) has been known to frequently express androgen receptor (AR). Therefore, androgens could play roles in the biological behavior of Paget cells. 5伪-Reductase (5伪-red) types 1 and 2 and 17尾-hydroxysteroid dehydrogenase type 5 (17尾-HSD5) are pivotal in situ regulators of androgen production in androgen-responsive tissues including androgen-dependent neoplasms. Therefore, in this study, we immunolocalized AR, androgen-producing enzymes, and their transcription factors to assess the state of in situ androgen production and actions and its correlation of invasiveness in EMPD. We studied 51 cases of EMPD with known clinicopathological status. AR, 5伪-red1, 17尾-HSD5, and 尾-catenin immunoreactivity was evaluated by using the modified H-score method while cyclin D1, p53, forkhead box protein P1, and a proliferation marker, Ki-67, were quantified using labeling index. The mean scores of AR, 5伪-red1, and 17尾-HSD5 in invasive EMPD were all significantly higher than noninvasive EMPD (P < .0001). Ki-67 labeling index as well as the cyclin D1 score was also significantly higher in invasive than noninvasive lesions of EMPD. These results demonstrated that androgen receptor and androgen-producing enzymes were both associated with cell cycle regulation and subsequently the invasiveness of EMPD lesions and could also indicate those above as potential markers of invasive potentials in EMPD.