Patients with advanced prostate cancer (PC) are usually treated with androgen withdrawal.
While this therapy is initially effective, nearly all PC become refractory to it. As hormone receptors play a crucial role in this process, we constructed a tissue microarray consisting of PC samples from 107 hormone naïve (HN) and 101 castration-resistant (CR) PC patients and analyzed the androgen receptor (AR) gene copy number, the protein expression profiles of AR, Serin210-phosphorylated AR (pAR210), estrogen receptor (ER)β, ERα and the proliferation marker Ki67. AR gene amplification was virtually restricted to CRPC and was significantly associated with increased AR protein expression (p< 0.0001) and higher tumor cell proliferation (p=0.001). Strong AR expression identified a subgroup of HN PC patients with adverse prognosis. In contrast, absence of AR expression in CR PC, was significantly associated with poor overall survival. While pAR210 was predominantly found in the CR PC (p< 0.0001), pAR210 positivity in HN PC patients identified a subgroup of patients with poor survival (p< 0.05). Epithelial ERα expression was restricted to CR PC cells (9%). ERβ protein expression was found in 38% of both HN and CR PCs, but was elevated in matched CR PC specimens. Similar to pAR210, the presence of ERβ in HN patients was significantly associated with adverse prognosis (p< 0.005). Our results strongly suggest a major role for pAR210 and ERβ in HN PC. Expression of these markers might be directly involved in CR tumor growth.
Written by:
Zellweger T, Stuerm S, Rey S, Zlobec I, Gsponer JR, Rentsch CA, Terracciano LM, Bachmann A, Bubendorf L, Ruiz C. Are you the author?
Department of Urology, St. Claraspital, Basel, Switzerland.
Reference: Endocr Relat Cancer. 2013 Apr 11. Epub ahead of print.
doi: 10.1530/ERC-12-0402
PubMed Abstract
PMID: 23580588
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