Androgen receptors in endocrine-therapy-resistant human prostate cancer

Abstract

Despite the initial androgen-dependent growth of most human prostate cancers, eventually all prostate cancers become androgen-independent at varying intervals after androgen ablation or anti-androgen therapy. In order to gain more insight into the role of the androgen receptor (AR) in this process, AR and prostate-specific antigen (PA) expression was evaluated immunohistochemically in prostatic tumour tissues from patients who developed urinary flow obstruction between 4 and 107 months after onset of treatment. AR expression was evaluated with a monoclonal antibody (MAb) specific for the N-terminal domain of the human AR. To substantiate the progressive tumour growth, proliferative activity was assessed immunohistochemically by staining with MAb Ki-67. Ki-67-defined tumour-growth fractions varied from 0.8-64.7%. In 13 of the 17 examined tumours over 80% of the tumour cells were AR-positive, 3 tumours showed a considerable heterogeneity in AR expression and in 1 tumour almost all tumour cells seemed to be AR-negative. Two-thirds of the examined tumours contained variable proportions of PA-positive tumour areas. These observations contrast with the view that androgen ablation induces a preferential outgrowth of receptor-negative tumour cells.