title: Androgen receptor, androgen-producing enzymes and their transcription factors in extramammary Paget disease.
abstract: 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. 5α-Reductase (5α-red) types 1 and 2 and 17β-hydroxysteroid dehydrogenase type 5 (17β-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, 5α-red1, 17β-HSD5, and β-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, 5α-red1, and 17β-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.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575 Japan; Faculty of Health Sciences, University Sultan Zainal Abidin, 21300 Kuala Terengganu, Terengganu, Malaysia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Azmahani
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575 Japan. Electronic address: yasu-naka@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575 Japan; Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575 Japan.
authors.forename: Keely M
authors.initials: KM
authors.lastname: McNamara
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Haga
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 980-8574 Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, 980-8575 Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010145:Paget Disease, Extramammary / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D011944:Receptors, Androgen; D012097:Repressor Proteins; D051176:beta Catenin; D019938:Cyclin D1; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase
keywords: Androgen receptor; Androgen-producing enzymes; Extramammary Paget's disease; Immunohistochemistry; Transcription factor