Objective To examine the role of androgen receptor (AR) gene amplification and aneusomy of the X chromosome in the development of antiandrogen‐resistant prostate cancer.

Patients and methods Twenty patients with prostate cancer resistant to androgen‐deprivation therapy were selected for study. The records of patients with tumours before and after antiandrogen therapy, and with a full clinical follow‐up, were retrieved. AR gene amplification and X chromosome copy number were assessed by fluorescence in situ hybridization using a labelled probe at locus Xq11–13 for the AR gene and a labelled α‐satellite probe for the X chromosome. At least 20 nuclei were scored over three tumour areas by two independent observers.

Results Aneusomy of the X chromosome was reported respectively in seven (35%) and 11 (55%) tumours before and after hormone relapse, the AR gene copy number was increased in seven (35%) and 13 (65%), respectively, and AR gene amplification was detected in one (5%) and three (15%), respectively. Neither increased AR copy number nor AR amplification in primary tumours precluded a biological response to androgen‐deprivation therapy.

Conclusion The rate of AR gene amplification is too low to be solely responsible for the development of antiandrogen‐resistant prostate cancer. Also, the presence of amplified AR and cells aneusomic for the X chromosome in primary tumours that respond to androgen‐deprivation therapy suggests that an increase in AR gene copy number does not prevent a tumour from responding to this therapy. Therefore other mechanisms which could cause hormone‐refractory prostate cancer must be investigated before it is understood why so many patients relapse with this disease.