Correlation of serum interleukin-6 (IL-6) levels with immunohistochemical p65/nuclear factor-κB (NF-κB) expression and prediction of the clinical outcome of hormone-independent prostate cancer patients (HIPC) treated with docetaxel (D)

Abstract

5075 Background: We have recently reported that NF-κB/IL-6 was linked to D response in human prostate cancer cells. In this study we investigated the clinical significance of IL-6 serum levels in HIPC pts treated with D and the correlation between serum IL-6 levels and p65/NF-κB tissue expression. Methods: Pts with HIPC treated with D were prospectively tested for IL-6 levels by ELISA before chemotherapy. In patients with available specimens of hormone-independent tumor p65/NF-κB was determined by immunohistochemistry. PSA response to D, time to progression and survival were analyzed. Results: Sixty pts were included. Median follow-up time was 29.3 (5.3–55.47) months. Median time to D progression was 4.2 (0,6–15.1) months and median survival was 10.1 (1.6- 47.1) months. Median baseline IL-6 were 16 pg/ml (range 0–156). Pts that responded to D had median IL-6 of 15.1±3.9 pg/ml and patients that did not respond had median IL-6 of 34.7±6.5 (p=0.009). IL-6 correlated with the number of bone metastasis (r=0.39, p=0.002), LDH levels (r=0.53, p<0.0001) and inversely with time to PSA progression (r=-0.65, p<0.0001) and survival (r=-0.61, p<0.0001). In the multivariate analysis IL-6 were an independent prognostic factor for time to PSA progression HR 1.026 (CI95% 1.013–1.046) and survival IL-6 levels HR 1.022 (CI 95% 1.006- 1.038, p=0.008). HIPC tissue samples from 12 pts were assessed for p65/NF-κB expression. All tissue samples showed cytoplasmatic and nuclear staining. Median percentage of nuclear p65/NF-κB stained cells was 15% (range 5–45%). P65/NF-κB nuclear staining showed correlation with serum IL-6 levels (r=0.719, p=0.009). Patients with low serum IL-6 levels (= 16 pg/ml) had a median % of nuclear p65/NF-κB staining of 5.4±2.5% and patients with high IL-6 levels had a median % of nuclear p65/NF-κB staining of 30.2±4.9% (p=0.001). Conclusions: High IL-6 serum levels were associated to a worse survival in HIPC pts treated with D. Our data suggest that the determination of serum IL-6 levels may serve as a surrogate marker of NF-κB activity in hormone-independent prostate cancer tumor and may be useful to select patients for NF-κB targeted therapy. No significant financial relationships to disclose.