Possible Role of HER-2 in the Progression of Prostate Cancer from Primary Tumor to Androgen Independence

Background: The expression of HER-2 in prostate cancer has been linked to disease progression. We analysedthe presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its associationwith clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) duringfollow up, as well as links with biochemical failure and the effects of androgen blockade. Materials and
Methods:Consecutive men undergoing radical prostatectomy for histologically confirmed prostate cancer were analyzed.HER-2 expression in the primary tumor was assessed using the HercepTest®, CPCs were identified from bloodsamples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest® todetermine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure andeffects of androgen blockade was determined.
Results: 144 men with a mean age of 64.8±10.3 years participated,with a median follow up of 8.2 years. HER-2 was expressed in 20.8% of primary tumors; it was associated withvascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men hadsecondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemicalfailure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. Afterandrogen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progressionto castrate resistant disease.
Conclusions: HER-2 plays a dual role in the progression of prostate cancer; firstlyit may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasingvascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but oncebiochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment,survive and grow leading to castration resistant disease.