Evaluation of dickkopf-1 (Dkk-1) expression in non-small cell lung, esophageal, and gastric cancer.

Abstract

e22203 Background: Dkk-1 is an inhibitor of the canonical Wnt/β-catenin signaling pathway. Inhibition of Wnt pathway results in the stabilization of β-catenin, leading to target gene expression such as cyclin D1, c-myc, VEGF and other factors associated with cell growth. Elevated levels of serum Dkk-1 in a variety of tumor types are well established, and are hypothesized to have a negative prognostic value. Tumor tissue expression of Dkk-1 has not been systematically examined. We evaluated Dkk-1 expression in various tumors. Methods: Utilizing an anonymous banked tumor repository, we identified 119 patient samples (NSCLC (squamous, n=19; adenocarcinoma, n=47), esophageal (squamous, n=15; adenocarcinoma, n=17) and gastric (n=20)). Immunohistochemical (IHC) staining was performed using commercially available antibodies. One pathologist evaluated all slides using IHC staining quantification on a 4-point scale (0, 1+, 2+, 3+). Results: Dkk-1 expression is more pronounced in tumor tissues than peritumoral normal tissues of lung and esophagus. Unexpectedly, Dkk-1 expression is seen in two staining patterns, perinuclear and cytoplasmic that varied by primary location and histology. Conclusions: Elevated Dkk-1 expression is demonstrated in lung, esophageal and gastric cancer regardless of histology. All except squamous cell lung express perinuclear Dkk-1 more frequently than cytoplasmic pattern. Additional studies are needed to understand significance of these patterns and potentially define Dkk-1 as a novel therapeutic target in these malignancies. [Table: see text]