Low Stroma Androgen Receptor Level in Normal and Tumor Prostate Tissue Is Related to Poor Outcome in Prostate Cancer Patients

BACKGROUND. The role of androgen receptors (ARs) in the prostate tumor cell environment is largely unknown. METHODS. AR immunostaining was evaluated in relation to stroma morphology, expression of AR co-activator ARA55, tumor characteristics and clinical outcome in normal and prostate cancer (PCa) tissue obtained at transurethral resection ill men treated with expectancy, and in diagnostic transrectal core biopsies in men treated with surgical castration. Stroma composition was studied by Masson-trichrome and desmin staining. Levels of AR and ARA55 mRNA were quantified by laser micro-dissection and RT-PCR. RESULTS. The percentage of cells with positive nuclear AR immunostaining in the tumor and normal stroma was inversely related to Gleason score, tumor size, tumor stage, metastasis, response to castration therapy, and cancer-specific survival. The AR staining in the normal stroma provided independent prognostic information in Cox multiple linear regression analysis. Loss of stroma AR staining was linked to low expression of ARA55 in stroma smooth muscle cells, and in tumors also to gradual disappearance of this cell type. CONCLUSIONS. PCa aggressiveness and efficacy of castration therapy are related to AR levels in the tumor stroma and importantly to AR levels in the surrounding normal prostate tissue stroma. Prostate 69: 799-809, 2009. (c) 2009 Wiley-Liss, Inc.