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Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 ± 16.6vs. 52.2 ± 6.2 ng/mL [p< 0.001]; VEGF, 55.1 ± 7.6vs. 32.1 ± 2.4 ng/mL [p< 0.001]; mean ± SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r= 0.556,p< 0.001) and VEGF levels (r= 0.335,p< 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9vs. 20 months [log-rank,p= 0.017]; median time to progression, 5vs. 10 months [log-rank,p= 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.