title: Prognostic and predictive value of YKL-40 in stage IIB-III melanoma.
abstract: This study investigates the prognostic and predictive value of YKL-40 in stage IIB-III melanoma patients who were randomized to adjuvant interferon α-2b (IFN) or observation. Serum YKL-40 was determined postoperatively in patients from the Nordic IFN Trial (n=602), EORTC 18952 (n=246), and EORTC 18991 (n=386) (EORTC, European Organisation for Research and Treatment of Cancer). YKL-40 protein expression was determined in 300 tissue sections of primary melanoma or lymph node metastases from 204 Danish patients from the Nordic IFN Trial. Multivariate Cox analysis (including sex, age, stage, ulceration, YKL-40) showed that elevated baseline YKL-40 level was associated with shorter overall survival (OS) in observation groups from the Nordic IFN Trial and EORTC 18952 [hazard ratio (HR)=1.33; 95% confidence interval (CI) 1.01-1.74; P=0.04], but not in the interferon groups (1-year IFN: HR=0.97; 95% CI 0.76-1.25; P=0.83; 2-years IFN: HR=1.06; 95% CI 0.83-1.34; P=0.64). During follow-up, increases in YKL-40 were significantly associated with shorter OS, but not with recurrence-free survival in univariate analysis. YKL-40 expression was stronger in tumor-associated macrophages than melanoma cells in primary melanoma. High YKL-40 expression in macrophages in lymph node metastases was associated with shorter OS in the observation group (HR=2.76; 95% CI: 1.13-6.76, P=0.02), but not in the interferon-treated groups. YKL-40 was an independent prognostic biomarker of OS in melanoma patients stage IIB-III. High serum YKL-40 in poor-prognosis patients may originate from macrophages in the tumor microenvironment and the melanoma cells. Furthermore, we hypothesize that elevated serum YKL-40 after surgery may predict the efficacy of adjuvant IFN treatment.
authors.affiliation: aDepartment of Oncology, Odense University Hospital, Odense C bThe Finsen Laboratory, Rigshospitalet, and Biotech Research and Innovation Centre, University of Copenhagen, København Departments of cOncology dMedicine ePathology, Herlev University Hospital, Herlev fAarhus University Hospital, Aarhus, Denmark gDepartment of Surgical Oncology, Erasmus University Medical Center-Daniel Den Hoed Cancer Center, Rotterdam, The Netherlands hKarolinska Institute, Stockholm, Sweden iEORTC Headquarters, Brussels, Belgium jGustave Roussy Cancer Institute, Villejuif, France.
authors.forename: Merete
authors.initials: M
authors.lastname: Krogh
authors.forename: Ib
authors.initials: I
authors.lastname: Christensen
authors.forename: Marna
authors.initials: M
authors.lastname: Bouwhuis
authors.forename: Julia S
authors.initials: JS
authors.lastname: Johansen
authors.forename: Peter
authors.initials: P
authors.lastname: Nørgaard
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
authors.forename: Johan
authors.initials: J
authors.lastname: Hansson
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Alexander M M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D000071451:Chitinase-3-Like Protein 1 / Q000097:blood*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins