Increased EpCAM expression in malignant insulinoma: potential clinical implications

Raffel, Andreas; Eisenberger, Claus Ferdinand; Cupisti, Kenko; Schott, M.; Baldus, Stephan; Hoffmann, Imke; Aydin, Feride; Knoefel, Wolfram Trudo; Stoecklein, Nikolas H.

doi:10.1530/eje-08-0916

Cited by 24 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…β-catenin is involved in the wnt signal pathways, and activates the expression of many target genes such as c-myc, vascular expressed EpCAM than adenomas (IPMAs). Some previous studies demonstrated that tumor cells expressed EpCAM more strongly in a process to acquire more invasive behaviors (4,20,26). Therefore, we speculated that EpCAM could play an important role in the invasive process of IPMNs.…”

Section: Discussionmentioning

confidence: 85%

Epithelial cell adhesion molecule (EpCAM) overexpression is correlated with malignant potentials of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas

et al. 2013

View full text Add to dashboard Cite

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas exhibit a wide range of histopathological variation. Epithelial cell adhesion molecule (EpCAM) is a 40 kDa type I membrane protein that is known to be highly expressed in epithelial carcinomas. In this study, we examined immunohistochemical expression of EpCAM in the pancreatic IPMNs in order to clarify its clinicopathological significance. We analyzed 51 cases of surgically resected IPMNs: 32 cases of adenoma; 6 cases of non-invasive carcinoma; 8 cases of minimally invasive carcinoma; and 5 cases of invasive carcinoma. Additionally, these 51 cases were classified into four phenotypes (gastric, intestinal, pancreatobiliary and oncocytic). EpCAM overexpression was found in 16 (31.4%) of the tumor samples. We found five predictive factors of malignancy using the univariate analysis as follows; serum CA19-9 level, main pancreatic duct diameter, presence of mural nodule, phenotype and EpCAM overexpression. In the multivariate analysis, only EpCAM overexpression was identified to be independently associated as a predictive factor for malignancy (odds ratio, 11.039; 95% confidence interval, 1.877-64.919; P-value, 0.008). Our study is the first report to demonstrate that EpCAM overexpression is an independent factor for malignancy; therefore, EpCAM overexpression is thought to be a novel predictor of malignant IPMNs.

show abstract

Section: Discussionmentioning

confidence: 85%

Epithelial cell adhesion molecule (EpCAM) overexpression is correlated with malignant potentials of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Studies testing HLA-B*1501 for presentation of EpCAM 140–148 are ongoing. Interestingly, EpCAM is known to be upregulated during islet development and in many tumor types including insulinomas, suggesting that T cell responses against autoantigens induced during islet regeneration may be significant markers for disease progression [21], [22]. While both T cell and autoantibody responses against EpCAM have been reported in cancer patients, there have been no previous reports of immune responses against either EpCAM or GLIPR1 in subjects with type I diabetes [23]–[25], highlighting the ability of synthetic minigene screening to identify truly novel antigens.…”

Section: Resultsmentioning

confidence: 99%

Discovery of T Cell Antigens by High-Throughput Screening of Synthetic Minigene Libraries

Hondowicz¹,

Schwedhelm²,

Kas³

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

The identification of novel T cell antigens is central to basic and translational research in autoimmunity, tumor immunology, transplant immunology, and vaccine design for infectious disease. However, current methods for T cell antigen discovery are low throughput, and fail to explore a wide range of potential antigen-receptor interactions. To overcome these limitations, we developed a method in which programmable microarrays are used to cost-effectively synthesize complex libraries of thousands of minigenes that collectively encode the content of hundreds of candidate protein targets. Minigene-derived mRNA are transfected into autologous antigen presenting cells and used to challenge complex populations of purified peripheral blood CD8+ T cells in multiplex, parallel ELISPOT assays. In this proof-of-concept study, we apply synthetic minigene screening to identify two novel pancreatic islet autoantigens targeted in a patient with Type I Diabetes. To our knowledge, this is the first successful screen of a highly complex, synthetic minigene library for identification of a T cell antigen. In principle, responses against the full protein complement of any tissue or pathogen can be assayed by this approach, suggesting that further optimization of synthetic libraries holds promise for high throughput antigen discovery.

show abstract

“…EpCAM upregulates c-myc and cyclins, promoting cell cycling and enhancing proliferation (20)(21)(22)(23)(24). Anti-EpCAM therapy has been trialed in metastatic breast cancer, colorectal cancer, and in malignant ascites (25)(26)(27)(28)(29)(30) and EpCAM expression in NETs presents an opportunity for EpCAM directed therapy (9). However, caution should be taken as normal pancreatic and intestinal tissue express EpCAM.…”

Section: Discussionmentioning

confidence: 99%

“…Its exact function is yet to be fully elucidated, but its expression enables the CellSearch platform to enrich CTCs via immunomagnetic separation with iron particles coupled to EpCAM antibodies. Although series have reported a small neuroendocrine subset of lung cancers (8) and insulinomas (9) to overexpress this epithelial marker, the systematic analysis of EpCAM expression in NETs has not been undertaken to our knowledge. Originally thought to be derived from cells of the neural crest sharing secretory and histologic properties with neural cells, it is debated whether NETs are epithelial in origin (10,11) and thus it has been assumed that CTCs cannot be isolated in NETs as they should not express EpCAM (12,13).…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cells and EpCAM Expression in Neuroendocrine Tumors

Khan

Tsigani

Rashid

et al. 2011

Clinical Cancer Research

103

View full text Add to dashboard Cite

Purpose: Neuroendocrine tumors (NET) are heterogeneous tumors with widely variable survival. It is unknown whether they express EpCAM (epithelial cell adhesion molecule) and thus whether NET circulating tumor cells (CTC) are detectable. We systematically investigated EpCAM expression and CTC detection in patients with metastatic NETs and evaluated the potential of CTCs to predict radiological progression.Experimental Design: EpCAM protein expression was evaluated in 74 samples of formalin-fixed, paraffin-embedded NET tissue by immunohistochemistry. Seventy-nine patients with metastatic NETs (42 midgut, 5 unknown primary, 19 pancreatic, 13 bronchopulmonary) had blood samples drawn for CTC isolation and enumeration utilizing the CellSearch platform. Patients were classified as having progressive or nonprogressive disease on the basis of serial imaging.Results: Strong homogeneous, membranous EpCAM expression was observed in all ileal (n ¼ 26) and pancreatic NETs (n ¼ 16), whereas variable EpCAM expression was observed in bronchopulmonary NETs (n ¼ 13). Forty-three percent of midgut and 21% of pancreatic NETs had CTCs detected with a range of 0-62 and 0-11, respectively. The absence of CTCs was strongly associated with stable disease (P < 0.001). There was a moderate correlation between CTC levels and urinary 5-hydroxyindole acetic acid (r ¼ 0.5, P ¼ 0.007) and between CTC levels and burden of liver metastases (B ¼ 8.91, P < 0.001). There was no or low correlation between CTC levels and Ki-67 (r ¼ 0.08, P ¼ 0.59) and serum chromogranin A (r ¼ 0.246, P ¼ 0.03).Conclusions: This is the first systematic analysis showing EpCAM expression and CTC detection in NETs. CTCs seem to be associated with progressive disease and may provide useful prognostic information given the variable survival rates in these tumors.

show abstract

Increased EpCAM expression in malignant insulinoma: potential clinical implications

Cited by 24 publications

References 26 publications

Epithelial cell adhesion molecule (EpCAM) overexpression is correlated with malignant potentials of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas

Epithelial cell adhesion molecule (EpCAM) overexpression is correlated with malignant potentials of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas

Discovery of T Cell Antigens by High-Throughput Screening of Synthetic Minigene Libraries

Circulating Tumor Cells and EpCAM Expression in Neuroendocrine Tumors

Contact Info

Product

Resources

About