Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers.
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-11-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2994724?pdf=render |
| _version_ | 1828761382689964032 |
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| author | Ranju Ralhan Helen C-H He Anthony K-C So Satyendra C Tripathi Manish Kumar Md Raghibul Hasan Jatinder Kaur Lawrence Kashat Christina MacMillan Shyam Singh Chauhan Jeremy L Freeman Paul G Walfish |
| author_facet | Ranju Ralhan Helen C-H He Anthony K-C So Satyendra C Tripathi Manish Kumar Md Raghibul Hasan Jatinder Kaur Lawrence Kashat Christina MacMillan Shyam Singh Chauhan Jeremy L Freeman Paul G Walfish |
| author_sort | Ranju Ralhan |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-11T01:28:31Z |
| format | Article |
| id | doaj.art-e21bb5ee622a44309f2c064fd93ef3b1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T01:28:31Z |
| publishDate | 2010-11-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-e21bb5ee622a44309f2c064fd93ef3b12022-12-22T01:25:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-11-01511e1413010.1371/journal.pone.0014130Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers.Ranju RalhanHelen C-H HeAnthony K-C SoSatyendra C TripathiManish KumarMd Raghibul HasanJatinder KaurLawrence KashatChristina MacMillanShyam Singh ChauhanJeremy L FreemanPaul G WalfishWe 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.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.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.http://europepmc.org/articles/PMC2994724?pdf=render |
| spellingShingle | Ranju Ralhan Helen C-H He Anthony K-C So Satyendra C Tripathi Manish Kumar Md Raghibul Hasan Jatinder Kaur Lawrence Kashat Christina MacMillan Shyam Singh Chauhan Jeremy L Freeman Paul G Walfish Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC2994724?pdf=render |
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