title: Androgen receptor modulation in benign human prostatic tissue and prostatic adenocarcinoma during neoadjuvant endocrine combination therapy.
abstract: Modulation of androgen receptor (AR) expression during neoadjuvant endocrine therapy in human prostates of patients with localized prostate cancer was investigated by immunohistochemistry. In 8 of 15 untreated prostatectomy specimens, the majority of prostatic glandular cells displayed nuclear immunostaining for AR, whereas only 1 of 26 pretreated cases displayed a similar glandular AR expression. Expression of AR in the prostatic stromal compartment of nontreated cases proved to be quite heterogeneous, since 4 of the 15 (27%) examined specimens did not show stromal AR expression. After preoperative neoadjuvant therapy, this value was 68%, although this difference did not reach statistical significance. Prostatectomy specimens of the treated patients contained carcinomas with a higher Gleason score than those of untreated patients. AR expression in carcinomas of treated patients was diminished (P= 0.05), which may be attributed to their relatively lower differentiation grade. The data strongly suggest that neoadjuvant hormone therapy reduces AR expression by nonneoplastic prostatic glandular cells and carcinoma cells by a selective, but incomplete, elimination of AR-positive cells.
authors.affiliation: Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
authors.forename: T H
authors.initials: TH
authors.lastname: Van der Kwast
authors.forename: B
authors.initials: B
authors.lastname: Têtu
authors.forename: Y
authors.initials: Y
authors.lastname: Fradet
authors.forename: A
authors.initials: A
authors.lastname: Dupont
authors.forename: J
authors.initials: J
authors.lastname: Gomez
authors.forename: L
authors.initials: L
authors.lastname: Cusan
authors.forename: P
authors.initials: P
authors.lastname: Diamond
authors.forename: F
authors.initials: F
authors.lastname: Labrie
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005485:Flutamide / Q000494:pharmacology / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D011944:Receptors, Androgen; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide