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Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers

BACKGROUND: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed t...

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Autores principales: Ralhan, Ranju, He, Helen C.-H., So, Anthony K.-C., Tripathi, Satyendra C., Kumar, Manish, Hasan, Md. Raghibul, Kaur, Jatinder, Kashat, Lawrence, MacMillan, Christina, Chauhan, Shyam Singh, Freeman, Jeremy L., Walfish, Paul G.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994724/
https://www.ncbi.nlm.nih.gov/pubmed/21152431
http://dx.doi.org/10.1371/journal.pone.0014130
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author Ralhan, Ranju
He, Helen C.-H.
So, Anthony K.-C.
Tripathi, Satyendra C.
Kumar, Manish
Hasan, Md. Raghibul
Kaur, Jatinder
Kashat, Lawrence
MacMillan, Christina
Chauhan, Shyam Singh
Freeman, Jeremy L.
Walfish, Paul G.
author_facet Ralhan, Ranju
He, Helen C.-H.
So, Anthony K.-C.
Tripathi, Satyendra C.
Kumar, Manish
Hasan, Md. Raghibul
Kaur, Jatinder
Kashat, Lawrence
MacMillan, Christina
Chauhan, Shyam Singh
Freeman, Jeremy L.
Walfish, Paul G.
author_sort Ralhan, Ranju
collection PubMed
description BACKGROUND: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers. METHODOLOGY AND RESULTS: Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers. CONCLUSIONS: Increased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and AUC. Development of a robust high throughput assay for Ep-ICD will facilitate the determination of its diagnostic, prognostic and therapeutic relevance in epithelial cancers.
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spelling pubmed-29947242010-12-08 Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers Ralhan, Ranju He, Helen C.-H. So, Anthony K.-C. Tripathi, Satyendra C. Kumar, Manish Hasan, Md. Raghibul Kaur, Jatinder Kashat, Lawrence MacMillan, Christina Chauhan, Shyam Singh Freeman, Jeremy L. Walfish, Paul G. PLoS One Research Article BACKGROUND: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers. METHODOLOGY AND RESULTS: Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers. CONCLUSIONS: Increased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and AUC. Development of a robust high throughput assay for Ep-ICD will facilitate the determination of its diagnostic, prognostic and therapeutic relevance in epithelial cancers. Public Library of Science 2010-11-30 /pmc/articles/PMC2994724/ /pubmed/21152431 http://dx.doi.org/10.1371/journal.pone.0014130 Text en Ralhan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ralhan, Ranju
He, Helen C.-H.
So, Anthony K.-C.
Tripathi, Satyendra C.
Kumar, Manish
Hasan, Md. Raghibul
Kaur, Jatinder
Kashat, Lawrence
MacMillan, Christina
Chauhan, Shyam Singh
Freeman, Jeremy L.
Walfish, Paul G.
Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers
title Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers
title_full Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers
title_fullStr Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers
title_full_unstemmed Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers
title_short Nuclear and Cytoplasmic Accumulation of Ep-ICD Is Frequently Detected in Human Epithelial Cancers
title_sort nuclear and cytoplasmic accumulation of ep-icd is frequently detected in human epithelial cancers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994724/
https://www.ncbi.nlm.nih.gov/pubmed/21152431
http://dx.doi.org/10.1371/journal.pone.0014130
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