Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients.
Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.
Crnalic
S
S
Department of Orthopedics, Umeå University, Umeå, Sweden.
Hörnberg
E
E
Wikström
P
P
Lerner
U H
UH
Tieva
A
A
Svensson
O
O
Widmark
A
A
Bergh
A
A
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary*; D053148:Caspase 3 / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D053379:Chromogranin A / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*
C410798:AR protein, human; D053379:Chromogranin A; D019394:Ki-67 Antigen; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen; D053148:Caspase 3