Serum IL-6 as a prognostic biomarker in patients with stage IIB-III melanoma.
8545 Background: Interleukin (IL)-6 is an immunomodulatory cytokine produced by cancer cells and different immune cells. The specific function of IL-6 in cancer is unknown. Serum IL-6 is elevated in patients with different types of cancer. Elevated serum concentration of IL-6 is related to short survival in patients with stage IV melanoma. Methods: IL-6 was measured by ELISA (R&D) in pretreatment serum samples from 435 patients with stage IIB-III melanoma (151 women and 284 men, median age 51 years, range 18-77). After surgery patients were treated in a randomized study (The Nordic IFN trial) with either adjuvant interferon for 1 or 2 years, or observation. Results: Median serum concentration of IL-6 after surgery and before treatment was 1.8 ng/l, range 0.23-24 ng/l. Patients with serum IL-6 above the median had shorter overall survival (OS) compared to patients with serum IL-6 below the median (p=0.004). Median OS was 4.5 years in patients with serum IL-6 above the median (95% confidence interval (CI): 3.05-7.60). In patients with serum IL-6 below the median, median OS was not reached at the last survival-update. Multivariate Cox analysis including serum IL-6, ulceration in primary melanoma, LDH, white blood cells, lymph node metastases and Breslow thickness of primary melanoma showed that only serum IL-6 (hazard ratio (HR) = 1.48, 95% confidence interval (CI) : 1.13-1.94, p=0.004) was an independent prognostic factor for OS. In subgroup analysis of the control group and the two treatment groups, serum IL-6 demonstrated a negative prognostic impact in the control group (HR = 1.62, 95% CI: 1.02-2.57, p=0.04) and in the group treated with 2 years interferon HR = 1.69, 95% CI: 1.06-2.7, p=0.03). In the group treated with 1 year interferon this negative impact was not significant (HR = 1.15, 95% CI: 0.71-1.85, p=0.58). An interaction between IL-6 and treatment arm was not significant (p=0.45), suggesting that the negative prognostic effect of elevated pretreatment serum IL-6 is independent of treatment. Conclusions: Serum IL-6 above the median is an independent prognostic biomarker of short OS in patients operated for stage IIB-III melanoma.