4.6 Article

Hyaluronan-mediated motility receptor (RHAMM) immunohistochemical expression and androgen deprivation in normal peritumoral, hyperplasic and neoplastic prostate tissue

Journal

BJU INTERNATIONAL
Volume 113, Issue 5, Pages 822-829

Publisher

WILEY-BLACKWELL
DOI: 10.1111/bju.12339

Keywords

RHAMM; hormonal resistance; androgen receptor; hyaluronan-mediated motility receptor; prostatic neoplasms; testosterone/antagonists and inhibitors; hyaluronic acid; cyproterone

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Objectives To evaluate hyaluronan-mediated motility receptor (RHAMM) expression in normal, hyperplasic and neoplastic prostate tissue after various types and durations of androgen-deprivation therapy (ADT). Clinical and oncological data from men with localised prostate adenocarcinoma were also assessed and compared with RHAMM expression data. Patients and Methods Data from 367 men who underwent histological evaluation of the prostate were retrospectively evaluated under six conditions: (i) benign prostatic hyperplasia (BPH), (ii) BPH treated with finasteride, (iii) prostate cancer without ADT, (iv) prostate cancer treated with neoadjuvant ADT before prostatectomy (cyproterone 200 mg/day), (v) castration-resistant prostate cancer (CRPC), and (vi) normal peritumoral prostate tissue. Tissue microarrays were constructed and 1354 cores were evaluated for immunohistochemical RHAMM expression. Results There was no RHAMM expression in any tissue from normal patients or those with BPH or prostate cancer without ADT. There was RHAMM expression in 39.4% of prostate cancer tissues treated with ADT and in 46.2% of CRPC samples (P = 0.001). There was a significant increase in RHAMM expression with increased ADT duration in group 4, with a marked increase in RHAMM expression after 6-12 months of ADT (P = 0.04). No prognostic or clinical factors related to prostate cancer were associated with RHAMM expression. Conclusions RHAMM expression in prostate cancer is directly associated with ADT. Significant RHAMM expression occurs as early as after 1 month of ADT and progressively increases with ADT duration. When prostate cancer becomes CRPC, RHAMM expression is higher. RHAMM expression was not associated with prostate cancer prognostic factors. RHAMM overexpression may contribute to the development of hormonal resistance in prostate cancer.

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