Originally published as JCO Early Release 10.1200/JCO.2005.03.7960 on January 3 2006

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Serum YKL-40 Predicts Relapse-Free and Overall Survival in Patients With American Joint Committee on Cancer Stage I and II Melanoma

From the Departments of Oncology, Plastic Surgery, and Clinical Biochemistry, Aarhus University Hospital; Department of Rheumatology, Herlev University Hospital, Herlev; and the Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre, Denmark

Address reprint requests to Henrik Schmidt, MD, Department of Oncology, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark; e-mail: hesch{at}as.aaa.dk

PURPOSE: To evaluate the novel tumor biomarker YKL-40 in serial serum samples from patients with American Joint Committee on Cancer (AJCC) stage I and II melanoma from the time of diagnosis and during routine follow-up. Macrophages, neutrophils, and cancer cells secrete YKL-40, and a high serum level has been associated with poor prognosis in patients with several cancer types.

PATIENTS AND METHODS: Serum samples from 234 patients with stage I (n = 162) and II (n = 72) melanoma were analyzed for YKL-40 by enzyme-linked immunosorbent assay. Serial samples were obtained before definitive primary surgery and during follow-up.

RESULTS: After a median follow-up period of 66 months (range, 1 to 97 months), 41 relapses (18%) and 39 deaths (17%) were observed. Serum YKL-40 treated as an updated continuous covariate were analyzed together with the covariates sex, age, primary tumor site, ulceration, thickness, Clark level and histologic subtype in a Cox proportional hazard model. Serum YKL-40 was an independent prognostic factor of relapse-free survival (hazard ratio [HR], 1.6; 95% CI, 1.1 to 2.5; P = .03) and overall survival (HR, 1.8; 95% CI, 1.2 to 2.6; P = .002) together with thickness and ulceration. The serum level of YKL-40 (dichotomized as normal or elevated) at the time of diagnosis was also an independent prognostic factor for overall survival (HR, 3.6, 95% CI, 1.7 to 7.7; P = .001).

CONCLUSION: Serum YKL-40 may be an early biomarker of relapse and survival in patients with AJCC stage I and II melanoma. Serum YKL-40 may also be useful for patient stratification and follow-up in clinical trials. Our results need confirmation in an independent study.

Supported by grants awarded by the Danish Cancer Society, "Direktor Jens Aage Sorensen og Hustru Edith Ingeborg Sorensens Mindefond," "Aase og Ejner Danielsens Fond," and "Radiumstationens forskningsfond."

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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