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Purpose: YKL-40 is a glycoprotein with a role in inflammation, tissue remodeling, tumor angiogenesis, and protection against apoptosis. We hypothesized that high preoperative plasma YKL-40 in patients with nonmetastatic bone and soft tissue sarcoma (STS) is associated with short overall survival (OS), and that plasma YKL-40 is an independent predictor for OS. Materials and methods: Plasma was collected preoperatively from 65 patients with nonmetastatic bone (n=14) or STS (n= 51) in the lower extremities (n= 43), the upper extremities (n=16) or the trunk wall/spine (n= 6). All patients underwent surgical cancer treatment. Twenty patients developed metastases during the follow-up period (minimum 5 y). The plasma concentration of YKL-40 was determined by enzyme-linked immunosorbent assay. Results: Twenty-seven patients died [mean: 3.2 (range: 0.2.7.3) y postoperatively] and 38 patients were still alive after a follow-up of mean 6.9 (5.8.8.2) years postoperatively. Plasma YKL-40 was higher in patients who died during follow-up (P=0.008), in males (P =0.007) and in patients 61 years of age and above (P= 0.001). The 5-year OS was 68% and OS was lower in patients with high (≥ 95% percentile age-corrected) plasma YKL-40 (P= 0.021), age 61 years and above (P =0.013), high histologic malignancy grade (P =0.047) and male sex (P= 0.051). Multivariable analysis showed that only plasma YKL-40 (age-corrected (hazard ratio =2.80, 95% confidence interval: 1.13.6.91, P=0.026) and malignancy grade (hazard ratio = 9.9 × 107, 95% confidence interval: 0–∞, P =0.007) remained independent prognostic factors for OS. Conclusions: High preoperative plasma YKL-40 was related to short OS in patients with nonmetastatic bone and STS and plasma YKL-40 (age-corrected) was an independent prognostic risk factor for OS.

Survival of patients with high-grade osteosarcoma (HOS), the most common primary bone cancer, has not improved significantly the last 30 years and the disease remains a major challenge. The purpose of this study is to evaluate survival in relation to prognostic factors at time of diagnosis among patients diagnosed with primary appendicular HOS in East Denmark between 1990 and 2010.101 patients (median age = 20 years, female/male ratio = 56/45) diagnosed with primary appendicular high-grade osteosarcoma between 1990 and 2010 were included in this study. Initially, 156 patients diagnosed with osteosarcoma between 1990 and 2010 were identified through the population based Regional Database of Pathology, which covers a population of approximately 2.7 million (east Denmark). 55 patients were excluded due to (A) tumor was low grade (n = 22), (B) located in axial skeleton (n = 18), (C) incorrect diagnosis (n = 11) or (D) biopsy represented a tumor relapse from a former primary osteosarcoma (n = 4). Overall survival was evaluated using the Kaplan-Meier survival analysis and log-rank test. Prognostic factors were analyzed using uni- and multivariate cox-regression method with variables scored equally in the model. p Values.05 were considered statistically significant.The probability of 5- and 10-year survival was 51% (95% CI: 41-61) and 46% (95% CI: 36-56), respectively. Metastatic stage at diagnosis and tumor size ≥10 cm measured radiologically at the largest diameter were independent prognostic factors for decreased survival with significant increased hazard-risks of 3.5 (95% CI: 1.9-6.5) and 1.97 (95% CI: 1.1-3.6), respectively.In this single institution evaluation of primary appendicular HOS we found 5-and 10-year survival rates consistent with international standards for this patient group. Distant metastases and tumor size ≥10 cm at the time of diagnosis were independent prognostic factors for decreased survival in our cohort. These results underline the importance of awareness and early referral from the primary sector.

YKL-40, a cellular glycoprotein isolated from the human osteosarcoma (OS) cell line MG63, is increased in the blood of patients with various types of cancer, and is found as an independent prognostic variable for survival. YKL-40 is also present with variable intensity in the tumor cells of some cancer types, but survival results have been conflicting. The aim of this study was to investigate the tissue expression of YKL-40 and its possible role as a predictive marker in patients with OS. Forty-eight patients were included in the study. Diagnostic biopsies were analyzed by immunohistochemistry; YKL-staining scores as well as CD14 and CD163 scores were determined, and survival data were determined statistically. A universal intense immunostaining for YKL-40 was found in all tumor cells, but tumor cell/stroma ratio varied, and this ratio (%) served as staining score. Using 24% as mean score to divide the material, patients with tumors of high YKL-40 score had a better survival than patients with low score (p = 0.05). YKL-positive macrophages had no influence on the result. Unexpectedly and contrary to some other findings in cancer tissues, this study has shown a correlation between high YKL-40 tumor cell/matrix ratio and longer overall survival in OS.