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Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis

Authors: Raj Thani Somasundaram, Jatinder Kaur, Iona Leong, Christina MacMillan, Ian J. Witterick, Paul G. Walfish, Ranju Ralhan

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Identification of patients with oral dysplasia at high risk of cancer development and oral squamous cell carcinoma (OSCC) at increased risk of disease recurrence will enable rigorous personalized treatment. Regulated intramembranous proteolysis of Epithelial cell adhesion molecule (EpCAM) resulting in release of its intracellular domain Ep-ICD into cytoplasm and nucleus triggers oncogenic signaling. We analyzed the expression of Ep-ICD in oral dysplasia and cancer and determined its clinical significance in disease progression and prognosis.

Methods

In a retrospective study, immunohistochemical analysis of nuclear and cytoplasmic Ep-ICD and EpEx (extracellular domain of EpCAM), was carried out in 115 OSCC, 97 oral dysplasia and 105 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 60 months for oral dysplasia and OSCC patients. Disease-free survival (DFS) was determined by Kaplan-Meier method and multivariate Cox regression analysis.

Results

In comparison with normal oral tissues, significant increase in nuclear Ep-ICD and membrane EpEx was observed in dysplasia, and OSCC (p = 0.013 and < 0.001 respectively). Oral dysplasia patients with increased overall Ep-ICD developed cancer in short time period (mean = 47 months; p = 0.044). OSCC patients with increased nuclear Ep-ICD and membrane EpEx had significantly reduced mean DFS of 33.7 months (p = 0.018).

Conclusions

Our study provided clinical evidence for Ep-ICD as a predictor of cancer development in patients with oral dysplasia and recurrence in OSCC patients, suggesting its potential utility in enhanced management of those patients detected to have increased risk of progression to cancer and recurrence in OSCC patients.
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Metadata
Title
Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis
Authors
Raj Thani Somasundaram
Jatinder Kaur
Iona Leong
Christina MacMillan
Ian J. Witterick
Paul G. Walfish
Ranju Ralhan
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2507-7

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