Elevated serum level of YKL‐40 is an independent prognostic factor for poor survival in patients with metastatic melanoma

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Abstract
BACKGROUND YKL‐40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. Cancer cells, macrophages, and neutrophils secrete YKL‐40. Its function in cancer is unknown. High serum YKL‐40 levels have been associated with a poor prognosis in patients with several solid tumors. The prognostic impact of serum YKL‐40 in metastatic melanoma was evaluated. METHODS YKL‐40 was measured in serial serum samples from 110 patients with metastatic melanoma obtained immediately before and during treatment and from 245 healthy subjects. RESULTS Patients had higher serum YKL‐40 values than healthy subjects (P < 0.001). Pretreatment serum YKL‐40 was elevated in 45% of the patients and correlated to site of metastases (P = 0.03) and poor performance status (P = 0.002). Multivariate Cox analysis showed that serum YKL‐40 (hazard ratio [HR] = 1.9; 95% confidence interval [CI], 1.2–2.8; P = 0.004) and serum lactate dehydrogenase (LDH) (HR = 1.9; 95% CI, 1.2–2.9; P = 0.004) were independent prognostic factors for survival. A combination variable of elevated serum YKL‐40 and LDH quadrupled the risk of early death (HR = 4.4; 95% CI, 2.5–7.7; P < 0.001) compared with patients with normal levels. The combination of YKL‐40 and LDH had a stronger prognostic impact than the American Joint Committee on Cancer (AJCC) Stage IV classification. Furthermore, serum samples were available from 12 patients during followup. In 9 of 11 patients a significant increase in serum YKL‐40 was observed together with disease progression. In one patient with a lasting complete response, serum YKL‐40 remained normal. CONCLUSIONS An elevated serum YKL‐40 was an independent prognostic factor for poor survival in patients with metastatic melanoma. When combining serum YKL‐40 and LDH, patients could be separated into three prognostic groups based on the number of elevated biomarkers. The findings should be validated in an independent study. Cancer 2006. © 2006 American Cancer Society.