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      EpCAM (CD326) finding its role in cancer

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      1 , * ,   2
      British Journal of Cancer
      Nature Publishing Group
      EpCAM, CD326, meeting report, role in cancer

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          Abstract

          Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future.

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          Most cited references39

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          Frequent EpCam protein expression in human carcinomas.

          Expression of the transmembrane glycoprotein EpCam (epithelial cellular adhesion molecule) occurs in normal epithelium of different organs and was described in carcinomas of various sites. Specific anti-EpCam therapies are now being used in clinical trials. Thus, it is of interest to know which tumor types express or overexpress this protein, and in what frequency. We therefore analyzed EpCam expression by immunohistochemistry on a tissue microarray containing 3900 tissue samples of 134 different histological tumor types and subtypes. EpCam expression was detected in 98 of 131 tumor categories. At least a weak EpCam expression in >10% of tumors was observed in 87 of 131 different tumor categories. Adenocarcinomas of the colon (81%) and pancreas (78%), as well as hormone-refractory adenocarcinomas of the prostate (71%), were identified as particularly promising therapy targets with a high fraction of strongly positive tumors. Most soft-tissue tumors and all lymphomas were EpCam negative. It is concluded that anti-EpCam therapies, if proven to be successful, will have broad applications in a wide variety of carcinomas.
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            EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy.

            EpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. EpCAM is involved in cell-to-cell adhesion and has been the target of antibody therapy in several clinical trials. To assess the value of EpCAM as a novel target for breast cancer gene therapy, we performed real-time reverse transcription-PCR to quantify the level of EpCAM mRNA expression in normal breast tissue and primary and metastatic breast cancers. We found that EpCAM is overexpressed 100- to 1000-fold in primary and metastatic breast cancer. Silencing EpCAM gene expression with EpCAM short interfering RNA (siRNA) resulted in a 35-80% decrease in the rate of cell proliferation in four different breast cancer cell lines. EpCAM siRNA treatment decreased cell migration by 91.8% and cell invasion by 96.4% in the breast cancer cell line MDA-MB-231 in vitro. EpCAM siRNA treatment was also associated with an increase in the detergent-insoluble protein fraction of E-cadherin, alpha-catenin, and beta-catenin, consistent with the known biology of EpCAM as a regulator of cell adhesion. Our hypothesis is that modulation of EpCAM expression can affect cell migration, invasion, and proliferation by enhancing E-cadherin-mediated cell-to-cell adhesion. These data provide compelling evidence that EpCAM is a potential novel target for breast cancer gene therapy and offer insights into the mechanisms associated with EpCAM gene silencing.
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              Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

              Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n=1186) of colon, 90.7% of gastric (n=473), and 87.2% of prostate cancers (n=414), and in 63.9% of lung cancers (n=1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (P<0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P=0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                09 January 2007
                06 February 2007
                12 February 2007
                : 96
                : 3
                : 417-423
                Affiliations
                [1 ]Micromet, Inc. 2110 Rutherford Road, Carlsbad, CA, 92008, USA
                [2 ]Clinical Cooperation Group Molecular Biology, GSF Research Center for Environment and Health, and Department for Head and Neck Research, Ludwig-Maximilians-University Marchioninistr. 15, Munich 81377, Germany
                Author notes
                [* ]Author for correspondence: Patrick.baeuerle@ 123456micromet-inc.com
                Article
                6603494
                10.1038/sj.bjc.6603494
                2360029
                17211480
                5ed96550-fcf3-4505-8aaa-bea6d277e2b2
                Copyright 2007, Cancer Research UK
                History
                : 14 July 2006
                : 27 September 2006
                : 10 October 2006
                Categories
                Clinical Studies

                Oncology & Radiotherapy
                epcam,role in cancer,meeting report,cd326
                Oncology & Radiotherapy
                epcam, role in cancer, meeting report, cd326

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