Background: Studies investigating serum midkine (s-MK) concentrations have employed a polyclonal antibody enzyme-linked immunosorbent assay system (ELISA), because the targeted polyclonal antibody has low specificity. We used a newly developed monoclonal antibody ELISA to investigate the prognostic and diagnostic capabilities of s-MK in patients with esophageal squamous cell carcinoma.
Methods: Serum samples from 102 patients with esophageal squamous cell carcinoma were analyzed using a newly developed monoclonal antibody ELISA specifically developed to detect s-MK. s-MK cutoff value was set at 421 pg/mL (mean + 2 SD) based on data from healthy controls. Clinicopathological characteristics, including tumor stage and positivity rates for two conventional tumor markers, serum p53 (s-p53-Abs) antibodies and SCC-antigen, were evaluated to assess a possible correlation with s-MK. The prognostic capability of a high s-MK level was evaluated using univariate and multivariate methods.
Results: Overall positive rate for s-MK concentrations: 21%. Large tumors (> 50 mm) showed significantly higher concentrations than smaller specimens, but other clinicopathological factors were not associated with s-MK. A combination assay using SCC-antigen together with s-p53-Abs and s-MK clearly increased our capability to detect esophageal squamous cell carcinoma. Although the difference was not statistically significant (P = 0.310), the high s-MK group experienced worse overall survival than our low s-MK group.
Conclusions: s-MK and conventional tumor marker combination increased our capability to detect esophageal squamous cell carcinoma. Although s-MK might be associated with esophageal squamous cell carcinoma progression, it was not an independent risk factor reducing patient survival. This study was registered as UMIN000014530.
Keywords: Biomarker; ELISA; Esophageal squamous cell carcinoma; Midkine; Monoclonal antibody.