Truncated Epcam is Associated with a More Aggressive Phenotype and Predicts Poor Overall Survival in Colorectal Cancer

Truncated Epcam is Associated with a More Aggressive Phenotype and Predicts Poor Overall Survival in Colorectal Cancer

Annals of Oncology 25 (Supplement 4): iv58–iv84, 2014 doi:10.1093/annonc/mdu326.52 biomarkers 218P TRUNCATED EPCAM IS ASSOCIATED WITH A MORE AGGRESS...

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Annals of Oncology 25 (Supplement 4): iv58–iv84, 2014 doi:10.1093/annonc/mdu326.52

biomarkers 218P

TRUNCATED EPCAM IS ASSOCIATED WITH A MORE AGGRESSIVE PHENOTYPE AND PREDICTS POOR OVERALL SURVIVAL IN COLORECTAL CANCER

abstracts

Aim: 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 and consequently upregulation of c-myc. Recently, we identified two different membranous EpCAM variants namely EpCAMMF and EpCAMMT to be expressed in the majority of human epithelial carcinomas. The aim of our study was to evaluate the potential of these two candidate protein biomarkers for identification of aggressive colorectal cancer. Methods: Using immunohistochemistry, we analyzed the expression of EpCAMMF and EpCAMMT variants in 632 patients with colorectal cancer and determined their correlations with other prognostic factors and clinical outcome. Results: A statistically significant association was observed for EpCAMMT with advanced tumor stage ( p < 0.001), histological grade ( p < 0.001), vascular ( p < 0.001) and marginal ( p < 0.001) invasion using chi-square test. Kaplan-Meier survival analysis demonstrated reduced overall survival ( p < 0.001) in patients showing the EpCAMMT phenotype when compared to patients with tumors expressing the EpCAMMF variant. Conclusions: In conclusion, this study indicates for the first time that expression of EpCAMMT is associated with a more aggressive phenotype and predicts poor survival in patients with colorectal cancer. Disclosure: All authors have declared no conflicts of interest.

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A. Seeber1, G. Spizzo2, L. Terracciano3, A. Lugli4, N. Steiner1, G. Mazzoleni5, G. Gastl1, D. Fong2 1 Hematology and Oncology, University Hospital Innsbruck, Innsbruck, AUSTRIA 2 Onco-haematologic Day Hospital, Ospedale Franz Tappeiner, Merano, ITALY 3 Pathology, University Hospital Basel, Basel, SWITZERLAND 4 Pathology, Translational Research Unit, Bern, SWITZERLAND 5 Pathology, Hospital of Bolzano, Bolzano, ITALY