HER-2/neu (p185neu) protein expression in the natural or treated history of prostate cancer

Abstract

Purpose: Amplification of HER-2/neu gene and overexpression of its encoded product, the p185neu (HER-2/neu) tyrosine kinase membrane receptor, have been associated with tumor progression in certain neoplasms. We conducted this study to investigate patterns of HER-2/neu protein expression in prostate cancer, analyzing different points in the natural and treated history of the disease.

Experimental design: Radical prostatectomy cases (83) and 20 metastatic lesions were studied for the association between HER-2/neu protein overexpression detected by immunohistochemistry and clinicopathological parameters, including time to prostate-specific antigen (PSA) relapse.

Results: HER-2/neu protein overexpression, defined as complete membrane staining in >10% of tumor cells using the Food and Drug Administration-approved Dako kit, was found in 9 of 45 (20%) of evaluable hormone naïve primary tumors and 23 of 34 (67%) primary tumors after androgen-deprivation therapy (P = 0.0001). Of the 20 metastatic lesions, positivity was noted in 16 (80%) of the cases. On univariate analysis, HER-2/neu overexpression was associated with pretreatment PSA (P = 0.011) and time to PSA relapse (P = 0.02). After controlling for pretreatment PSA, the association between hormone treatment and HER-2/neu was still observed. No association was found between HER-2/neu overexpression and Gleason score, capsular invasion, and tumor proliferative index determined by Ki67.

Conclusions: These data suggest that there is significant HER-2/neu overexpression in primary tumors that persist after androgen deprivation. It also emphasizes the importance of characterizing tumors at determined points in the natural or treated history of prostate cancer when targeting treatment to specific biological processes.