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

Seeber, Andreas; Untergasser, Gerold; Spizzo, Gilbert; Terracciano, Luigi; Lugli, Alessandro; Kasal, Armin; Kocher, Florian; Steiner, Normann; Mazzoleni, Guido; Gastl, Guenther; Fong, Dominic (2016). Predominant expression of truncated EpCAM is associated with a more aggressive phenotype and predicts poor overall survival in colorectal cancer. International journal of cancer, 139(3), pp. 657-663. Wiley-Blackwell 10.1002/ijc.30099

[img] Text
ijc30099.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (322kB) | Request a copy

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Terracciano, Luigi and Lugli, Alessandro

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0020-7136

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

23 Dec 2016 09:40

Last Modified:

23 Dec 2016 09:40

Publisher DOI:

10.1002/ijc.30099

PubMed ID:

26996277

Uncontrolled Keywords:

EpCAM; EpICD; colorectal cancer; immunohistochemistry; intracellular domain of EpCAM

BORIS DOI:

10.7892/boris.92071

URI:

https://boris.unibe.ch/id/eprint/92071

Actions (login required)

Edit item Edit item
Provide Feedback