Serum c-erbB-2 ectodomain (ECD) correlates with immunohistochemical c-erbB-2 expression and predicts an aggressive clinical outcome in hormone-independent prostate cancer (HIPC) patients (pts) treated with docetaxel (D)

Abstract

4632 Background: The overexpression of c-erbB-2 has been described as a common event associated to the hormone-independent progression in prostate cancer. The clinical implications of c-erbB-2 expression in HIPC pts are not fully established. In this study we investigated the clinical significance of c-erbB-2 serum levels in HIPC pts treated with D and the correlation between serum c-erbB-2 ECD and c-erbB-2 tissue expression. Methods: Pts with HIPC treated with D were tested for serum c-erbB-2 ECD levels by immunoassay before chemotherapy. In pts with available biopsy specimens of hormone-independent tumor, c-erbB-2expression was determined by immunohistochemistry in paraffin-embedded tissue sections. PSA response to D, time to PSA progression and survival were analyzed. Results: Forty-one pts were included in the study. Median follow-up time was 23.3 (3.7–43.1) months. Median time to D progression was 4.1 (0,4–15.1) months and median survival was 11.3 (1,6–43.1). Serum c-erbB-2 correlated with PSA (r=0.351, p=0.025), inversely with time to PSA progression (r = −0.338, p = 0.033) and inversely with survival (r = −0.305, p = 0.05). Median time to PSA progression in pts with high serum c-erbB-2 (≥15 ng/ml) was 1.5 months compared to 4.6 months in pts with low levels (p = 0.0003). Survival in pts with high c-erbB-2 was 11 months and in pts with low c-erbB-2 was 15 months (p = 0.053). HIPC tissue samples from 10 pts were assessed for c-erbB-2 expression. Immunohistochemical c-erbB-2 positive staining (score +2 and +3) was detected in 4 (40%). C-erbB-2 staining showed correlation with serum c-erbB2 levels. Pts with positive staining had 19.1 ± 1.78 ng/ml and negative pts 8.8 ± 2.6 ng/ml (p = 0.001).The 4 pts with tissue c-erbB-2 overexpression had serum c-erbB-2 levels >15 ng/ml, while pts with no c-erbB-2 overexpression in tissue had also low c-erbB-2 levels in serum. Conclusions: High c-erbB-2 ECD in serum is associated with a worse clinical outcome of HIPC. Our data suggest that the determination of c-erbB-2 ECD in serum translates the c-erbB-2 status in the hormone-independent tumor and may be useful to select pts for c-erbB-2-targeted therapy. No significant financial relationships to disclose.