title: Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer.
abstract: 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.
authors.affiliation: Tyrolean Cancer Research Institute, Innsbruck, Austria.|Oncotyrol-Center for Personalized Cancer Medicine, Innsbruck, Austria.|Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Seeber
authors.affiliation: Tyrolean Cancer Research Institute, Innsbruck, Austria.|Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
authors.forename: Gerold
authors.initials: G
authors.lastname: Untergasser
authors.affiliation: Tyrolean Cancer Research Institute, Innsbruck, Austria.|Oncotyrol-Center for Personalized Cancer Medicine, Innsbruck, Austria.|Department of Haematology and Oncology, Medical University of Innsbruck, Austria.|Haemato-Oncological Day Hospital, Hospital of Merano, Italy.
authors.forename: Gilbert
authors.initials: G
authors.lastname: Spizzo
authors.affiliation: Molecular Pathology Division, Institute of Pathology, University of Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.affiliation: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lugli
authors.affiliation: Department of Pathology, Central Hospital of Bolzano, Italy.
authors.forename: Armin
authors.initials: A
authors.lastname: Kasal
authors.affiliation: Tyrolean Cancer Research Institute, Innsbruck, Austria.|Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Kocher
authors.affiliation: Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
authors.forename: Normann
authors.initials: N
authors.lastname: Steiner
authors.affiliation: Department of Pathology, Central Hospital of Bolzano, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Mazzoleni
authors.affiliation: Department of Haematology and Oncology, Medical University of Innsbruck, Austria.
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
authors.affiliation: Tyrolean Cancer Research Institute, Innsbruck, Austria.|Oncotyrol-Center for Personalized Cancer Medicine, Innsbruck, Austria.|Department of Haematology and Oncology, Medical University of Innsbruck, Austria.|Haemato-Oncological Day Hospital, Hospital of Merano, Italy.
authors.forename: Dominic
authors.initials: D
authors.lastname: Fong
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D000071858:Epithelial Cell Adhesion Molecule
keywords: EpCAM; EpICD; colorectal cancer; immunohistochemistry; intracellular domain of EpCAM