Members of the EpCAM signalling pathway are expressed in gastric cancer tissue and are correlated with patient prognosis

Br J Cancer. 2013 Oct 15;109(8):2217-27. doi: 10.1038/bjc.2013.536. Epub 2013 Sep 5.

Abstract

Background: We investigated the expression of members of the epithelial cell adhesion molecule (EpCAM) signalling pathway in gastric cancer (GC) testing the following hypotheses: are these molecules expressed in GC and are they putatively involved in GC biology.

Methods: The study cohort consisted of 482 patients. The following members of the EpCAM signalling pathway were analysed by immunohistochemistry and were correlated with various clinico-pathological patient characteristics: extracellular domain of EpCAM (EpEX), intracellular domain of EpCAM (EpICD), E-cadherin, β-catenin, presenilin-2 (PSEN2), and ADAM17.

Results: All members of the EpCAM signalling pathway were differentially expressed in GC. The expression correlated significantly with tumour type (EpEX, EpICD, E-cadherin, β-catenin, and PSEN2), mucin phenotype (EpEX, EpICD, β-catenin, and ADAM17), T-category (EpEX, E-cadherin, and β-catenin), N-category (EpEX and β-catenin), UICC tumour stage (EpEX, EpICD, β-catenin, and PSEN2), tumour grade (EpEX, EpICD, E-cadherin, β-catenin, and PSEN2), and patients' survival (EpEX, EpICD, and PSEN2). A significant coincidental expression in GC was found for EpEX, EpICD, E-cadherin, β-catenin, PSEN2, and ADAM17. Decreased immunodetection of EpEX in locally advanced GC was not associated with decreased EpCAM mRNA levels.

Conclusion: All members of the EpCAM signalling pathway are expressed in GC. The expression correlated significantly with each other and with various clinico-pathological patient characteristics, including patients' survival. Thus, the EpCAM signalling pathway is a highly interesting putative therapeutic target in GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / biosynthesis
  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • ADAM17 Protein
  • Aged
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cohort Studies
  • Epithelial Cell Adhesion Molecule
  • Female
  • HEK293 Cells
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Staging
  • Presenilin-2 / biosynthesis
  • Presenilin-2 / genetics
  • Presenilin-2 / metabolism
  • Prognosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Signal Transduction
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • beta Catenin / biosynthesis
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Antigens, Neoplasm
  • CTNNB1 protein, human
  • Cadherins
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • PSEN2 protein, human
  • Presenilin-2
  • RNA, Messenger
  • beta Catenin
  • ADAM Proteins
  • ADAM17 Protein
  • ADAM17 protein, human