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Cancer Sci. 2003 Jul;94(7):628-32.

Preoperative serum midkine concentration is a prognostic marker for esophageal squamous cell carcinoma.

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Department of Academic Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8677, Japan.


High preoperative serum midkine concentration is associated with poor survival in patients with esophageal cancer, even after radical surgery, and thus may have prognostic value. Midkine (MK), a heparin-binding growth factor, is expressed in numerous cancer tissues, and serum MK (S-MK) concentrations are increased in patients with various neoplasms. The aim of this study is to evaluate the clinical significance of S-MK in patients with esophageal squamous cell cancer (SCC). S-MK was measured by enzyme-linked immunosorbent assay in 135 healthy controls, 16 patients with benign esophageal disease, and 93 patients with primary esophageal SCC before surgery. The serum concentrations of carcinoembryonic antigen (CEA), SCC antigen (SCC-Ag), and cytokeratin 19 fragment (CYFRA21-1) were also evaluated. All patients with esophageal SCC underwent radical esophagectomy. Tumor MK expression was assessed by immunohistochemistry in 14 fresh tumor specimens. To determine whether S-MK is of value as a prognostic factor, the authors conducted a survival analysis using Cox's proportional hazards model. S-MK values in patients with esophageal SCC were significantly higher than those in healthy controls (417 +/- 342 pg/ml vs. 154 +/- 76 pg/ml, P < 0.001). Using 300 pg/ml as the cut-off value (representing the mean + 2 standard deviations of the S-MK of healthy controls), 61% of patients with esophageal SCC were classified as positive. MK expression by the tumor was significantly associated with high level of S-MK. High S-MK (>/= 300 pg/ml) was associated with tumor size, immunoreactivity and poor survival. Multivariate analysis indicated that S-MK was an independent prognostic factor. S-MK may be a useful tumor marker for esophageal SCC. Increased preoperative S-MK in patients with esophageal SCC is associated with poor survival.

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