TY - JOUR
T1 - Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers
AU - Ralhan, Ranju
AU - He, Helen C.H.
AU - So, Anthony K.C.
AU - Tripathi, Satyendra C.
AU - Kumar, Manish
AU - Hasan, Md Raghibul
AU - Kaur, Jatinder
AU - Kashat, Lawrence
AU - Macmillan, Christina
AU - Chauhan, Shyam Singh
AU - Freeman, Jeremy L.
AU - Walfish, Paul G.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78649763769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649763769&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0014130
DO - 10.1371/journal.pone.0014130
M3 - Article
C2 - 21152431
AN - SCOPUS:78649763769
SN - 1932-6203
VL - 5
JO - PloS one
JF - PloS one
IS - 11
M1 - e14130
ER -