Abstract. YKL-40 (human cartilage glycoprotein-39) is a member of family 18 glycosyl hydrolases. YKL-40 is a growth factor and is secreted by cancer cells. High serum levels of YKL-40 in patients with colorectal cancer and recurrent metastatic breast cancer have been associated with a poor prognosis. We evaluated the prognostic value of plasma YKL-40 in patients with primary ovarian cancer (OC). YKL-40 was determined by ELISA in plasma obtained preoperatively from 47 women with stage III OC and in plasma from 79 healthy females. The results showed that plasma YKL-40 was elevated compared to healthy females in 57% of the OC patients and was highest in the patients who died during the follow-up compared to the patients still alive (186 vs. 78 μg/l, p=0.002). Patients with high plasma YKL-40 (>130 μg/l) had significantly (p=0.0003) shorter survival than patients with normal plasma YKL-40. Multivariate Cox regression analysis showed that plasma YKL-40 (RH=3.95; 95% CI, 1.52-10.27; p=0.005) and radicality after primary surgery (RH=4.03; 95% CI, 1.81-8.97; p=0.001) were independent prognostic factors of survival, whereas age, histological type of tumour and serum CA125 had no independent prognostic value. In conclusion, plasma levels of YKL-40 proved of prognostic value in stage III OC patients. Introduction Ovarian cancer (OC) is the fifth most frequent female cancer type and the fourth most frequent cause of death from cancer among women in Denmark in spite of extensive therapy (1). At the time of diagnosis about 70% of patients have advanced cancer [The International Federation of Gynecology and Obstetrics (FIGO) stage III or IV]. Published five-year survival rates for OC patients range from 80% for stage I cancer to <20% for stage III and IV (2,3). Although many prognostic factors have been found in OC (4-7), no reliable method for identification of nonresponders to therapy has been described so far. Clearly, the need for useful prognostic factors in order to optimise treatment of the patients diagnosed with OC has to be emphasized. YKL-40 is a mammalian member of family 18 glycosyl hydrolases (8-10). YKL-40 is a heparin and chitin binding protein (9,11) but has no chitinase activity (8,11). The exact function of YKL-40 is unknown, but it has recently been shown that YKL-40 is a growth factor for connective tissue cells (12) (Recklies AD, et al, Arthritis Rheum 43: abs. 1686, 2000) and is a potent migration factor for endothelial cells (13). Furthermore, the pattern of its expression in normal and disease state suggests a role in inflammation and remodeling of the extracellular matrix. The protein has been termed YKL-40 from its molecular weight (40 kDa) and the one- letter code for its three N-terminal amino acids (14). The gene has been sequenced, but promotor analysis and regulatory factors have not been described (15). YKL-40 is secreted in large amounts in vitro by the MG63 human osteosarcoma cell line (14) and is expressed selectively by murine mammary tumours initiated by neu/ras oncogenes (10). A search of the YKL-40 protein sequence against the dbest database at the NCBI using the BLAST program has shown that several types of cancer cells, including ovarian cancer, express the protein. ONCOLOGY REPORTS 10: 1535-1538, 2003 High plasma YKL-40 level in patients with ovarian cancer stage III is related to shorter survival * ESTRID V. S. HØGDALL 1,2 , JULIA S. JOHANSEN 3 , SUSANNE K. KJAER 1 , PAUL A. PRICE 7 , LISE CHRISTENSEN 4 , JAN BLAAKAER 6 , JOHANNES E. BOCK 5 , EVA GLUD 1 and CLAUS K. HØGDALL 5 1 Institute of Cancer Epidemiology, Danish Cancer Society; 2 Laboratory of Molecular Biology, Statens Serum Institute; Departments of 3 Rheumatology, Hvidovre Hospital and 4 Pathology, Rigshospitalet, University of Copenhagen; 5 The Gynaecologic Clinic, The Juliane Centre, Rigshospitalet, University of Copenhagen, Copenhagen; 6 Department of Gynaecology and Obstetrics, Aarhus University Hospital, Skejby, Denmark; 7 Department of Biology, University of California San Diego, La Jolla, CA, USA Received November 12, 2002; Accepted December 30, 2002 _________________________________________ Correspondence to: Dr Estrid Høgdall, Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark E-mail: hogdall@dadlnet.dk * From the Danish ‘MALOVA’ ovarian cancer study Abbreviations: OC, ovarian cancer; FIGO, The International Federation of Gynecology and Obstetrics; RH, relative hazard; CI, confidence interval; NOS, not otherwise specified Key words: YKL-40, ovarian cancer, survival, prognostic factors