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


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.
Division of Urology, ABC Medical School, São Paulo, Brazil.
Fernando
F
Korkes
Marilia Germanos
MG
de Castro
Stenio
S
de Cassio Zequi
Lívia
L
Nardi
Auro
A
Del Giglio
Antonio Carlos
AC
de Lima Pompeo
D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005500:Follow-Up Studies; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011468:Prostatectomy; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D012189:Retrospective Studies
D000726:Androgen Antagonists; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; C098946:hyaluronan-mediated motility receptor
RHAMM; androgen receptor; cyproterone; hormonal resistance; hyaluronan-mediated motility receptor; hyaluronic acid; prostatic neoplasms; testosterone/antagonists and inhibitors