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Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions

Oncogene volume 24, pages 6626–6636 (2005)Cite this article

Abstract

Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumours. Both the late clinical presentation of patients, due to lack of early symptoms, as well as the rapid and aggressive course of the disease contribute to the extremely high mortality of this malignancy. Recently, a multistep progression model for PDAC integrating morphological, clinical and molecular evidence has been proposed. Putative precursor lesions, termed pancreatic intraepithelial neoplasia (PanIN), are classified into three different grades (PanIN-1 through -3) based on the degree of cellular atypia they display. We have conducted large-scale expression profiling analyses of microdissected cells from normal pancreatic ducts, PanINs of different grades and PDACs using whole-genome oligonucleotide microarrays. Verification of hybridisation results for selected genes was performed using quantitative real-time PCR and immunohistochemical analyses on PanIN tissue microarrays. Comparison of the expression profiles demonstrated that the greatest changes in gene expression occur between PanIN stages 1B and 2, suggesting that PanIN-2 may represent the first truly preneoplastic stage in PDAC progression. Our results identify a large number of potential target genes for the development of novel molecular diagnostic and therapeutic tools for the prevention and early diagnosis of PDAC and provide novel insights into the pathophysiological mechanisms involved in tumour progression in the pancreas.

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Acknowledgements

We thank Susanne Braun, Karin Lanz, Claudia Ruhland, Pat Schreiter and Britta Redeker for excellent technical assistance. The work of the GPCN is supported by a multicentre grant form the Deutsche Krebshilfe, Bonn, Germany.

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Author notes

  1. Malte Buchholz, Mike Braun, Anna Heidenblut, Hans A Kestler, Günter Klöppel, Wolff Schmiegel, Stephan A Hahn, Jutta Lüttges and Thomas M Gress: Malte Buchholz, Mike Braun and Anna Heidenblut: These authors contributed equally to this work and should be considered joint first authors

  2. Stephan A Hahn, Jutta Lüttges and Thomas M Gress: These authors contributed equally to this work and should be considered joint senior authors

  3. The German Pancreatic Cancer Net is a consortium funded by the Deutsche Krebshilfe composed of the following groups at German institutes: S Hahn and W Schmiegel, Department of Internal Medicine, University of Bochum; G Klöppel and J Lüttges, Institute of Pathology, University of Kiel; TM Gress, M Braun and M Buchholz, Department of Internal Medicine, University Hospital of Ulm; H Schäfer and H Müller, Institute of Biometry and Epidemiology, University of Marburg; HE Meyer, Proteome Center, University of Bochum; DK Bartsch and M Rothmund, Department of Visceral Surgery, University of Marburg; P Möller and C Hasel, Department of Pathology, University Hospital of Ulm; D Henne-Bruns and U Knippschild, Department of Surgery, University Hospital of Ulm; M Lerch, Department of Internal Medicine, University of Greifswald; H Kalthof, Department of Surgery, University of Kiel; R Moll, Department of Pathology, University of Marburg; W Bechstein, Department of Surgery, University of Bochum

Authors and Affiliations

  1. Department of Internal Medicine I, University Hospital of Ulm, Robert Koch Str. 8, Ulm, 89081, Germany

    Malte Buchholz, Mike Braun, Hans A Kestler & Thomas M Gress

  2. Department of Internal Medicine, University of Bochum, Bochum, Germany

    Anna Heidenblut, Wolff Schmiegel & Stephan A Hahn

  3. Department of Pathology, University of Kiel, Kiel, Germany

    Günter Klöppel & Jutta Lüttges

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  1. Malte Buchholz
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Buchholz, M., Braun, M., Heidenblut, A. et al. Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions. Oncogene 24, 6626–6636 (2005). https://doi.org/10.1038/sj.onc.1208804

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Keywords

  • PanIN progression
  • gene expression
  • early diagnosis
  • target genes

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