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Early Detection and Prognosis of Ovarian Cancer Using Serum YKL-40

From the Developmental Chemotherapy Service, Department of Medicine; Clinical Genetics Service; Departments of Surgery, Neurology, and Cell Biology; Department of Epidemiology and Biostatistics; and Department of Laboratory Science, Memorial Sloan-Kettering Cancer Center; and Joan and Sanford I. Weill Medical College of Cornell University, New York, NY

Address reprint requests to Jakob Dupont, MD, Memorial Sloan-Kettering Cancer Center, Howard 905, 1275 York Ave, New York, NY 10021; e-mail: dupontj{at}mskcc.org

PURPOSE: YKL-40 is a secreted glycoprotein (chitinase family). We compared YKL-40 with two ovarian cancer serum markers, CA125 and CA15-3, for the detection of early-stage ovarian cancer.

MATERIALS AND METHODS: Serum YKL-40 levels were assayed by enzyme-linked immunosorbent assay for 46 healthy subjects, 61 high-risk individuals, 33 patients with benign gynecologic processes, and 50 preoperative patients subsequently diagnosed with predominantly early-stage ovarian cancer. Serum CA125 and CA15-3 values were obtained.

RESULTS: Median YKL-40 level was 28 ng/mL (range, 15 to 166 ng/mL) for healthy subjects, 36 ng/mL (range, 9 to 69 ng/mL) for high-risk individuals without prior cancer, 44.5 ng/mL (range, 5 to 133 ng/mL) for high-risk patients with prior breast cancer, and 38 ng/mL (range, 5 to 67 ng/mL) for individuals with benign gynecologic processes (P = NS). Median preoperative YKL-40 level for ovarian cancer patients was 94 ng/mL (range, 17 to 517 ng/mL; P < .0001 compared with normal and high-risk). YKL-40 was elevated ( 62 ng/mL) in 36 (72%) of 50 patients compared with 23 (46%) of 50 and 13 (26%) of 50 patients for CA125 and CA15-3 (P < .008). Twenty (65%) of 31 early-stage patients had elevated serum YKL-40 levels compared with 11 (35%) of 31 and four (13%) of 31 patients for CA125 and CA15-3 (P = .039). YKL-40 levels increased with stage (P < .005), regardless of grade, histology, or patient age. Patients with early-stage tumors with YKL-40 values more than 80 ng/mL had a worse prognosis (71% recurrence v no recurrence [P = .034]).

CONCLUSION: YKL-40 may represent a novel marker for the detection of early-stage ovarian cancer. YKL-40 levels in early-stage patients may also predict disease recurrence and survival. The utility of YKL-40 in detection of early-stage ovarian cancer deserves further investigation.

Supported by the Society of Memorial Sloan-Kettering Cancer Prevention Control and Population Science Program Grant, American Society of Clinical Oncology Young Investigator (YIA) and Career Development (CDA) Awards (J.D.), Epithelial Ovarian Program Project (NIH: PO1 CA52477-12), and The Eileen Genet Fund.

Jakob Dupont and Meena K. Tanwar contributed equally to the manuscript.

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

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