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Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer.

  • Seeber A Tyrolean Cancer Research Institute, Innsbruck, Austria.
  • Untergasser G Tyrolean Cancer Research Institute, Innsbruck, Austria.
  • Spizzo G Tyrolean Cancer Research Institute, Innsbruck, Austria.
  • Terracciano L Molecular Pathology Division, Institute of Pathology, University of Basel, Switzerland.
  • Lugli A Translational Research Unit (TRU), Institute of Pathology, University of Bern, Switzerland.
  • Kasal A Department of Pathology, Central Hospital of Bolzano, Italy.
  • Kocher F Tyrolean Cancer Research Institute, Innsbruck, Austria.
  • Steiner N Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
  • Mazzoleni G Department of Pathology, Central Hospital of Bolzano, Italy.
  • Gastl G Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
  • Fong D Tyrolean Cancer Research Institute, Innsbruck, Austria.
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  • 2016-03-22
Published in:
  • International journal of cancer. - 2016
EpCAM
EpICD
colorectal cancer
immunohistochemistry
intracellular domain of EpCAM
Aged
Aged, 80 and over
Biomarkers, Tumor
Colorectal Neoplasms
Epithelial Cell Adhesion Molecule
Female
Gene Expression
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Staging
Phenotype
Prognosis
Tissue Array Analysis
English Regulated intramembrane proteolysis (RIP) has been shown to be an important mechanism for oncogenic activation of EpCAM through nuclear translocation of the intracellular domain EpICD. Recently, we identified two different membranous EpCAM variants namely EpCAM(MF) (full-length) and EpCAM(MT) (truncated) to be expressed in the majority of human epithelial tumors. The aim of our study was to evaluate the potential role of these two protein variants as additional prognostic biomarkers in colorectal cancer. In most studies only one antibody targeting the extracellular domain of EpCAM (EpEX) has been used, whereas in the present study additionally an antibody which detects the intracellular domain (EpICD) was applied to discriminate between different EpCAM variants. Using immunohistochemistry, we analyzed the expression of EpCAM(MF) and EpCAM(MT) variants in 640 patients with colorectal cancer and determined their correlations with other prognostic factors and clinical outcome. A statistically significant association was observed for EpCAM(MT) with advanced tumor stage (p < 0.001), histological grade (p = 0.01), vascular (p < 0.001) and marginal (p = 0.002) invasion. Survival analysis demonstrated reduced overall survival (p < 0.004) in patients with tumors expressing the EpCAM(MT) phenotype when compared to patients with tumors expressing the EpCAM(MF) variant. In conclusion, this study for the first time indicates that expression of EpCAM(MT) is associated with a more aggressive phenotype and predicts poor survival in patients with colorectal cancer.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/206370
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