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 I 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.