Immunohistochemically detectable dickkopf-3 expression in tumor vessels predicts survival in gastric cancer

Virchows Arch. 2010 Jun;456(6):635-46. doi: 10.1007/s00428-010-0926-4. Epub 2010 May 15.


Dickkopf-3 (Dkk-3) may act as a tumor suppressor as it is downregulated in various types of cancer. Moreover, a putative role in tumor neovascularization is discussed. Here, we investigated the expression of Dkk-3 protein in gastric cancer and its potential value as a prognostic marker. Dkk-3 expression was analyzed by immunohistochemistry in 136 tumor samples and was correlated with microvessel density (MVD), tumor stage, and grading as well as the clinical outcome of the patients. Dkk-3 expression was detected in endothelial cells of the tumor vessels in 129/136 (94.9%) and in tumor cells in 85/136 (62.5%) samples. MVD was high and low in 57 (42.9%) and 76 (57.1%) specimens respectively. In tumor cells, overexpression of Dkk-3 was found in 41 (30.1%) of all cases and was correlated significantly to pT-stage (p < 0.05) and UICC stage (p < 0.05). Survival analysis regarding Dkk-3 expression in tumor endothelial cells showed that Dkk-3 is an independent predictor of disease-free survival (p < 0.05). Dkk-3 expression in tumor vessels of patients with gastric cancer identifies a population of patients with relatively favorable prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood supply
  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Chemokines
  • Endothelial Cells / chemistry
  • Female
  • Humans
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / analysis*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Stomach Neoplasms / blood supply
  • Stomach Neoplasms / chemistry*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology


  • Biomarkers, Tumor
  • Chemokines
  • DKK3 protein, human
  • Intercellular Signaling Peptides and Proteins