Abstract
YKL‐40 is a glycoprotein secreted by macrophages, neutrophils and malignant tumor cells. Elevated serum levels of YKL‐40 are associated with poor prognosis in several malignancies. In this study, we examined the prognostic value of serum YKL‐40 before treatment and during follow‐up in patients with squamous cell carcinoma of the head and neck (HNSCC). YKL‐40 was determined by ELISA retrospectively in serum from 173 patients with primary HNSCC before treatment and up to 2 years after treatment. Median follow‐up time was 7.9 years. YKL‐40 protein expression in tumor biopsies was assessed by immunohistochemistry in 50 patients. Pretreatment serum YKL‐40 was elevated in 53%. Patients with high serum YKL‐40 had shorter survival than patients with normal serum YKL‐40 (33 vs. 84 months; p = 0.008). Multivariate Cox analysis including pretreatment serum YKL‐40, age, sex, primary tumor site, TNM classification and treatment demonstrated that TNM classification (HR = 2.61, p = 0.02) and serum YKL‐40 (log‐transformed continuous variable: HR = 1.55, p < 0.0001) were independent prognostic variables of overall survival (OS). Multivariate Cox analysis demonstrated that TNM classification (HR = 5.77, p = 0.001) and serum YKL‐40 (dichotomous variable: HR = 2.75, p = 0.01) were independent predictors of recurrence‐free survival. During follow‐up after radiotherapy, a high serum YKL‐40 (log‐transformed continuous variable) in patients with TNM Stage III and IV disease predicted poorer OS within 6 months (HR = 1.95, p < 0.0001). Immunohistochemical analysis showed YKL‐40 expression in the malignant tumor cells. In conclusion, serum YKL‐40 was demonstrated to be an independent prognostic biomarker of recurrence‐free and overall survival in patients with HNSCC. © 2007 Wiley‐Liss, Inc.