Elevated levels of HER‐2/ neu and androgen receptor in clinically localized prostate cancer identifies metastatic potential

BACKGROUND In this study, we investigated the expression of HER‐2/ neu and AR in clinically organ‐confined prostate cancer to determine whether alterations in these signaling pathways contribute to the development of metastatic disease. METHODS HER‐2/ neu and AR immunoreactivity were evaluated in archived prostatic tissues obtained from 53 men with clinically organ‐confined disease who underwent radical prostatectomy. Associations between AR and HER‐2/ neu immunostaining and disease outcome were determined. RESULTS Seventy percent (37/53) of tumors exhibited high levels of HER‐2/ neu immunostaining and 68% (36/53) of tumors had elevated AR levels. Patients with high levels of both HER‐2/ neu and AR had the highest rate of PSA failure (56%, 15/27) compared with no PSA failures amongst seven patients with low levels of both HER‐2/ neu and AR (log rank statistic 7.69, P  = 0.021). Concurrent high levels of HER‐2/ neu and AR expression were significantly associated with high pathological stage ( P  = 0.027) and development of metastatic disease ( P  = 0.022). CONCLUSIONS These findings support the notion that both the HER‐2/ neu and AR signaling pathways may contribute to development of metastatic disease. The subset of prostate tumors with increased HER‐2/ neu and AR levels may benefit from treatment strategies that target both signaling pathways. Prostate 68:830–838, 2008. © 2008 Wiley‐Liss, Inc.