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Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947324/ https://www.ncbi.nlm.nih.gov/pubmed/27421772 http://dx.doi.org/10.1186/s12885-016-2507-7 |
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author | Somasundaram, Raj Thani Kaur, Jatinder Leong, Iona MacMillan, Christina Witterick, Ian J. Walfish, Paul G. Ralhan, Ranju |
author_facet | Somasundaram, Raj Thani Kaur, Jatinder Leong, Iona MacMillan, Christina Witterick, Ian J. Walfish, Paul G. Ralhan, Ranju |
author_sort | Somasundaram, Raj Thani |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4947324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49473242016-07-17 Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis Somasundaram, Raj Thani Kaur, Jatinder Leong, Iona MacMillan, Christina Witterick, Ian J. Walfish, Paul G. Ralhan, Ranju BMC Cancer Research Article 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. BioMed Central 2016-07-16 /pmc/articles/PMC4947324/ /pubmed/27421772 http://dx.doi.org/10.1186/s12885-016-2507-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Somasundaram, Raj Thani Kaur, Jatinder Leong, Iona MacMillan, Christina Witterick, Ian J. Walfish, Paul G. Ralhan, Ranju Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis |
title | Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis |
title_full | Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis |
title_fullStr | Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis |
title_full_unstemmed | Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis |
title_short | Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis |
title_sort | subcellular differential expression of ep-icd in oral dysplasia and cancer is associated with disease progression and prognosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947324/ https://www.ncbi.nlm.nih.gov/pubmed/27421772 http://dx.doi.org/10.1186/s12885-016-2507-7 |
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