Abstract
The expression of HER-2 in prostate cancer has been linked to disease progression. We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade. 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 blood samples using standard immunocytochemistry with anti-PSA and positive samples with the HercepTest® to determine HER-2 expression. The influence of HER-2 expression on the frequency of biochemical failure and effects of androgen blockade was determined. 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 with vascular infiltration and older age, but not with other clinical pathological findings. Some 40.3% of men had secondary CPCs detected, of which 38% expressed HER-2. Men CPC (+) had a higher frequency of biochemical failure, but there was no difference in HER-2 expression of CPCs with the frequency of biochemical failure. After androgen blockade, men with HER-2 (+) positive secondary CPCs had a higher frequency of disease progression to castrate resistant disease. HER-2 plays a dual role in the progression of prostate cancer; firstly it may increase the potential of tumor cells to disseminate from the primary tumor via the blood by increasing vascular infiltration. In the presence of androgens, there is no survival advantage of expressing HER-2, but once biochemical failure has occurred and androgen blockade started, HER-2 positive cells are resistant to treatment, survive and grow leading to castration resistant disease.
Highlights
There is evidence linking the expression of HER-2 in prostate cancer to disease progression and the development of androgen independent disease
We analysed the presence of HER-2 expression in primary tumors in men undergoing radical prostatectomy, its association with clinical and pathological findings, and its expression in secondary circulating prostate cells (CPCs) during follow up, as well as links with biochemical failure and the effects of androgen blockade
HER-2 has been proposed as a survival factor for prostate cells in the absence of androgens, possibly by activating the androgen receptor (Craft et al, 1999; Signoretti et al, 2000; Osman et al, 2001)
Summary
There is evidence linking the expression of HER-2 in prostate cancer to disease progression and the development of androgen independent disease. There is a suggestion that HER-2 may have a role in prostate cancer development, its expression is variable, ranging between 0 to 100% depending on the HER-2 assay used (Ratan et al, 2003) and gene amplification of the HER-2 gene ranges from 0 to 53% (Liu et al, 2001; Montironi et al, 2006). Despite this discrepancy, there is still a consistent association between HER-2 over expression and a higher risk tumor recurrence and death in men with prostate cancer according to a meta-analysis (Neto et al, 2010). Asian Pacific Journal of Cancer Prevention, Vol 16, 2015 6615 expression of HER-2 in the primary tumor, the expression of HER-2 in secondary circulating prostate cells (CPCs) after radical prostatectomy, its association with the clinical pathological findings and its influence on the occurrence of biochemical failure and the effect of androgen blockade
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