Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers

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

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32 Scopus citations

Abstract

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 domainspecific 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.

Original languageEnglish (US)
Article numbere14130
JournalPloS one
Volume5
Issue number11
DOIs
StatePublished - Dec 10 2010

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Ralhan, R., He, H. C. H., So, A. K. C., Tripathi, S. C., Kumar, M., Hasan, M. R., Kaur, J., Kashat, L., Macmillan, C., Chauhan, S. S., Freeman, J. L., & Walfish, P. G. (2010). Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers. PloS one, 5(11), [e14130]. https://doi.org/10.1371/journal.pone.0014130