The biology of the 17-1a antigen (Ep-CAM)

Department of Pathology, Leiden University Medical Center, The Netherlands.
Journal of Molecular Medicine (Impact Factor: 5.11). 11/1999; 77(10):699-712. DOI: 10.1007/s001099900038
Source: PubMed


The glycoprotein recognized by the monoclonal antibody (mAb) 17-1A is present on most carcinomas, which makes it an attractive target for immunotherapy. Indeed, adjuvant treatment with mAb 17-1A did successfully reduce the 5 years mortality among colorectal cancer patients with minimal residual disease. Currently the antibody is approved for clinical use in Germany, and is on its way to approval in a number of other countries. New immunotherapeutic strategies targeting the 17-1A antigen are in development or even in early-phase clinical trials. Therefore, a better understanding of the biology of the 17-1A antigen may result in improved strategies for the treatment and diagnosis of human carcinomas. In this review the properties of the 17-1A antigen are discussed concerning tumor biology and the function of the molecule. This 40-kDa glycoprotein functions as an Epithelial Cell Adhesion Molecule, therefore the name Ep-CAM was suggested. Ep-CAM mediates Ca2+-independent homotypic cell-cell adhesions. Formation of Ep-CAM-mediated adhesions has a negative regulatory effect on adhesions mediated by classic cadherins, which may have strong effects on the differentiation and growth of epithelial cells. Indeed, in vivo expression of Ep-CAM is related to increased epithelial proliferation and negatively correlates with cell differentiation. A regulatory function of Ep-CAM in the morphogenesis of epithelial tissue has been demonstrated for a number of tissues, in particular pancreas and mammary gland. The function of Ep-CAM should be taken into consideration when developing new therapeutic approaches targeting this molecule.

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    • "Amino acid sequences encoded by exon 1 correspond to a signal peptide sequence, while exons 2 to 6 encode sequences that form the extracellular domain. The transmembrane region is encoded by exon 7, and the 15-amino acid portion of the cytoplasmic domain, including a cluster of six positively charged amino acids, is encoded by exon 8. Exon 9 encodes the remaining 13 amino acids of the cytoplasmic domain, the stop codon, and the 3'-un- translated region (Balzar et al., 1999). GA733-2 plays an important role in the regulation of cell adhesion (Zanna et al., 2007). "
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    ABSTRACT: GA733-1/-2/-3 genes have been detected in various types of cancer, although their role has not been fully clarified. GA733-2 and GA733-1 have been correlated with lymph node metastases in laryngeal cancer and liver metastases, respectively. Only a few studies have elucidated the mechanisms regulating GA733-1/-2 expression and their effect on colorectal cancer. Therefore, the expression pattern and the role of the aforementioned molecules in colorectal carcinogenesis were evaluated in this study. Tissue samples were obtained from 40 patients with colorectal cancer with no liver metastases. GA733-1/-2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. GA733-1/-2 gene expression in noncancerous/cancerous tissues was also correlated with clinicopathological parameters. The GA733-1 mRNA levels were very low; however, the GA733-1 mRNA transcripts were higher in cancerous tissues than in normal tissues (median ratio, 0.004391/0.00093; range, 0.000001- 0.025139/0.000001-0.007761), respectively (P = 0.012). GA733-2 gene expression was higher in noncancerous tissues than in cancerous tissues (median ratio 273.31/115.64; range, 65.24-1,486.41/11.58-1,189.14; P = 0.0000195). Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples; conversely, the GA733-2 mRNA levels were higher in noncancerous tissues, and were significantly correlated with lymph node perforation in colorectal cancer (P < 0.05). Therefore, GA733-1/-2 mRNA expression levels appear to be a potential predictive marker of tumorigenesis.
    Preview · Article · Nov 2015 · Genetics and molecular research: GMR
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    • "Data for the study was collected with a functionalized and structured medical wire (FSMW) [19] that is a CE-certified medical device for the isolation of CTCs. Human carcinoma cells expresses the epithelial cell adhesion molecule (EpCAM) on their surface while this molecule is absent from the surface of haematological cells [20] [21] [22]. The FSMW is functionalized with anti-EpCAM antibodies and was inserted into the cubital vein of a patient through a standard 20 G intravenous cannula, where it was left for 30 minutes collecting CTCs from the blood that flows past [19]. "
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    ABSTRACT: Application of personalized medicine requires integration of different data to determine each patient’s unique clinical constitution. The automated analysis of medical data is a growing field where different machine learning techniques are used to minimize the time-consuming task of manual analysis. The evaluation, and often training, of automated classifiers requires manually labelled data as ground truth. In many cases such labelling is not perfect, either because of the data being ambiguous even for a trained expert or because of mistakes. Here we investigated the interobserver variability of image data comprising fluorescently stained circulating tumor cells and its effect on the performance of two automated classifiers, a random forest and a support vector machine. We found that uncertainty in annotation between observers limited the performance of the automated classifiers, especially when it was included in the test set on which classifier performance was measured. The random forest classifier turned out to be resilient to uncertainty in the training data while the support vector machine’s performance is highly dependent on the amount of uncertainty in the training data. We finally introduced the consensus data set as a possible solution for evaluation of automated classifiers that minimizes the penalty of interobserver variability.
    Full-text · Article · Oct 2015 · Journal of Immunology Research
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    • "The most highly conserved regions are the thyroglobulin repeat domain and the transmembrane region. Unlike, Trop2, which is intronless, Epcam consists of nine coding exons; Exons 1–6 encode the extracellular domain, exon 7 the transmembrane region, and exons 8–9 the intracellular tail (Balzar et al., 1999). The cysteine positions and distributions of hydrophilic and hydrophobic residues in the thyroglobulin repeat domain are conserved between TROP2 and EpCAM. "

    Full-text · Dataset · Feb 2015
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