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Expression and nuclear localization of Snail, an E-cadherin repressor, in adenocarcinomas of the upper gastrointestinal tract

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Abstract

Transcriptional E-cadherin down-regulation can be mediated by Snail, a zinc finger transcription factor. To be able to examine nuclear Snail immunoreactivity in archival human cancers, we established a monoclonal antibody against the purified human Snail protein. The specificity of the selected rat antibody Sn9H2 was demonstrated by Western blot analysis using extracts from different cell lines and by immunofluorescence and immunohistochemistry of primary tissues. Subsequently, a series of 340 adenocarcinomas of the upper gastrointestinal tract, including tumours from the oesophagus (n=154), cardia (n=102) and stomach (n=84), arranged in tissue microarrays, were examined for Snail expression and were correlated to E-cadherin expression and clinico-pathological parameters. Nuclear Snail immunoreactivity was seen in 27 tumours (7.9%) and tended to be more frequent in oesophageal adenocarcinomas (11.1%) than in cardiac (6.9%) or gastric (3.6%) carcinomas (p=0.0428). In 35% of the Snail-positive cases, E-cadherin immunoreactivity was lost. No correlation was found for nuclear Snail expression and tumour grade, Lauren’s classification, WHO classification, tumour stage and tumour size. The pattern of Snail expression observed with our new hybridoma, Sn9H2, which is currently the only antibody that reacts with endogenous nuclear (active) Snail, suggests only a minor role of Snail in tumours of the upper gastrointestinal tract.

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Acknowledgements

We thank M. Blöchinger and M. Bekesch for excellent technical assistance, J. Mages for providing the modified pHAT vector, and R. Langer for help with some tissues. The E-cadherin-positive gastric cancer cell line GC2957 was kindly provided by R. Seruca, IPATIMUP-Porto. This work is supported by a grant from the Deutsche Krebshilfe (grant no. 10-2012-Be3) to KFB and HH.

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  1. Erika Rosivatz

    Present address: Department of Biological Sciences, Imperial College London, London, SW7 2AY, UK

Authors and Affiliations

  1. Institut für Pathologie, Technische Universität München, Trogerstrasse 18, 81675, München, Germany

    Erika Rosivatz, Karl-Friedrich Becker, Christina Schott, Kareen Blechschmidt, Heinz Höfler & Mario Sarbia

  2. Institute of Molecular Immunology, GSF-National Research Centre for Environment and Health, Marchioninistrasse 25, 81377, München, Germany

    Elisabeth Kremmer

  3. Institute of Pathology, GSF-National Research Centre for Environment and Health, 85764, Neuherberg, Germany

    Heinz Höfler

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  1. Erika Rosivatz
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Correspondence to Karl-Friedrich Becker.

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Rosivatz, E., Becker, KF., Kremmer, E. et al. Expression and nuclear localization of Snail, an E-cadherin repressor, in adenocarcinomas of the upper gastrointestinal tract. Virchows Arch 448, 277–287 (2006). https://doi.org/10.1007/s00428-005-0118-9

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