Purpose: Amplification of HER-2/neu gene and overexpression of its encoded
product, the p185neu (HER-2/neu) tyrosine kinase membrane receptor, have be
en associated with tumor progression in certain neoplasms. We conducted thi
s study to investigate patterns of HER-2/neu protein expression in prostate
cancer, analyzing different points in the natural and treated history of t
Experimental Design: Radical prostatectomy cases (83) and 20 metastatic les
ions were studied for the association between HER-2/neu protein overexpress
ion detected by immunohistochemistry and clinicopathological parameters, in
cluding time to prostate-specific antigen (PSA) relapse.
Results: HER-2/neu protein overexpression, defined as complete membrane sta
ining in > 10% of tumor cells using the Food and Drug Administration-approv
ed Dako kit, was found in 9 of 45 (20%) of evaluable hormone naive 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 assoc
iated with pretreatment PSA (P = 0.011) and time to PSA relapse (P = 0.02).
After controlling for pretreatment PSA, the association between hormone tr
eatment and HER-2/neu was still observed. No association was found between
HER-2/neu overexpression and Gleason score, capsular invasion, and tumor pr
oliferative index determined by Ki67.
Conclusions: These data suggest that there is significant HER-2/neu overexp
ression 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.