LUNG CANCER

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors

H Kothmaier¹, F Quehenberger², I Halbwedl¹, P Morbini³, F Demirag⁴, H Zeren⁵, C E Comin⁶, B Murer⁷, P T Cagle⁸, R Attanoos⁹, A R Gibbs⁹, F Galateau-Salle¹⁰, H H Popper¹

¹ Institute of Pathology, Statistics and Documentation, Medical University of Graz, Austria
² Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Austria
³ Instituto di Anatomia Patologica, IRCCS Policlinico S Matteo, Pavia, Italy
⁴ Department of Pathology, Atatürk Chest Disease and Chest Surgery Education and Research Hospital, Ankara, Turkey
⁵ Pathology, Adana University, Adana, Turkey
⁶ Department of Human Pathology and Oncology, University of Florence, Italy
⁷ Department of Anatomic Pathology, Mestre, Italy
⁸ Department of Pathology, The Methodist Hospital and Cornell University Houston, Houston, Texas, USA
⁹ Department of Histopathology, Cardiff and Vale NHS Trust, Llandough Hospital, Penarth Vale of Glamorgan, Cardiff, UK
¹⁰ Laboratoire d’Anatomie Pathologique, CHU Cote de Nacre, Caen Cedex, France

Dr H H Popper, Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, A-8036 Graz, Austria; helmut.popper{at}meduni-graz.at

Background: 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.

Methods: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology.

Results: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was 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.

Conclusion: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?