Androgen receptor gene amplification and protein expression in hormone refractory prostate cancer.

Abstract

This study examined androgen receptor (AR) gene amplification and protein expression in 102 matched paired hormone sensitive and resistant tumours from 51 patients. AR gene amplification and X chromosome copy number were assessed by fluorescent in situ hybridisation, and protein expression was assessed by immunohistochemistry. All tumours were stained for PSA protein expression. Significantly more tumours exhibited AR amplification following the development of hormone resistance (20%, 10 out of 49) compared to matched hormone-sensitive tumours from the same patient (2%, one out of 48) (P=0.0085). The level of AR expression was significantly higher in hormone-resistant tumours compared to matched hormone-sensitive tumours from the same patient (130, interquartile range, 55–167 vs 94.5 interquartile range, 55–120, P=0.019). AR expression levels in hormone-resistant tumours with and without AR amplification were not significantly different. However, an increase in AR expression was seen with the development of AR amplification in paired tumours. The rate of AR gene amplification and/or an increase in AR protein expression during androgen resistant is too low to wholly explain the development of androgen resistance. Alternative mechanisms for modulating the function of the AR, or other signalling pathways, must be considered as key factors in the development of hormone-resistant prostate.