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EGFR And PDGFR Differentially Promote Growth In Malignant Epitheloid Mesothelioma Of Short- And Long-term Survivors
  1. Hannelore Kothmaier (hannelore.kothmaier{at}meduni-graz.at)
  1. Institute of Pathology, Medical University of Graz, Austria
    1. Franz Quehenberger (franz.quehenberger{at}meduni-graz.at)
    1. Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria
      1. Iris Halbwedl (iris.halbwedl{at}meduni-graz.at)
      1. Institute of Pathology, Medical University of Graz, Austria
        1. Patricia Morbini (p.morbini{at}smatteo.pv.it)
        1. Instituto di Anatomia Patologica, IRCCS Policlinico S. Matteo, Pavia, Italy
          1. Funda Demirag (halukfunda{at}superposta.com)
          1. Dept. Pathology,Atatürk Chest Disease and Chest SurgeryEducation and Research Hospital, Ankara, Turkey
            1. Handan Zeren (ehandanzeren{at}yahoo.com)
            1. Pathology, Adana University, Adana, Turkey
              1. Camilla E Comin
              1. Department of Human Pathology and Oncology, University of Florence, Florence, Italy
                1. Bruno Murer (brmurer{at}tin.it)
                1. Dept of Anatomic Pathology, Ospedale Umberto, Mestre, Italy
                  1. Philip T Cagle (pcagle{at}tmh.tmc.edu)
                  1. Department of Pathology, The Methodist Hospital & Cornell University Houston, United States
                    1. Richard Attanoos (richard.attanoos{at}cardiffandvale.wales.nhs.uk)
                    1. Department of Histopathology, Cardiff and Vale NHS Trust Llandough Hospital, Cardiff, United Kingdom
                      1. Allen R. Gibbs (allenrg{at}btinternet.com)
                      1. Department of Histopathology, Cardiff and Vale NHS Trust Llandough Hospital, Cardiff, United Kingdom
                        1. Francoise Gallateau-Salle (galateausalle-f{at}chu-caen.fr)
                        1. 10Laboratoire d'Anatomie Pathologique CHU Cote de Nacre, Caen Cedex, France
                          1. Helmut H. Popper (helmut.popper{at}meduni-graz.at)
                          1. Institute of Pathology, Medical University of Graz, Austria

                            Abstract

                            Malignant pleural mesothelioma (MPM) is an asbestos-related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short-term survivors (survival <3 years; STS) and long-term survivors (survival >3 years; LTS) of MPM. In order to do this, 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, anti-apoptosis, angiogenesis, and other cellular activities were investigated by tissue microarray (TMA) technology. Epidermal growth factor receptor (EGFR) is expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling is more abundant in STS. The expression of TIE2/Tek, a receptor tyrosine kinases involved in angiogenesis, is differentially regulated via PDGFR and thus is more important in STS. Anti-apoptosis is upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. We demonstrate that small scale proteomics can be carried out by a powerful linkage of TMA, immunohistochemistry, and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.

                            • Mesothelioma
                            • immunohistochemistry
                            • short- and long-term survivors
                            • signal pathways
                            • tissue microarray

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