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Differentiation of multiple types of pancreatico-biliary tumors by molecular analysis of clinical specimens

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Abstract

Timely and accurate diagnosis of pancreatic ductal adenocarcinoma (PDAC) is critical in order to provide adequate treatment to patients. However, the clinical signs and symptoms of PDAC are shared by several types of malignant or benign tumors which may be difficult to differentiate from PDAC with conventional diagnostic procedures. Among others, these include ampullary cancers, solid pseudopapillary tumors, and adenocarcinomas of the distant bile duct, as well as inflammatory masses developing in chronic pancreatitis. Here, we report an approach to accurately differentiate between these different types of pancreatic masses based on molecular analysis of biopsy material. A total of 156 bulk tissue and fine needle aspiration biopsy samples were analyzed using a dedicated diagnostic cDNA array and a composite classification algorithm developed based on linear support vector machines. All five histological subtypes of pancreatic masses were clearly separable with 100% accuracy when using all 156 individual samples for classification. Generalized performance of the classification system was tested by 10 × 10-fold cross validation (100 test runs). Correct classification into the five diagnostic groups was demonstrated for 81.5% of 1,560 test set predictions. Performance increased to 85.3% accuracy when PDAC and distant bile duct carcinomas were combined in a single diagnostic class. Importantly, overall sensitivity of detection of malignant disease was 92.2%. The molecular diagnostic approach presented here is suitable to significantly aid in the differential diagnosis of undetermined pancreatic masses. To our knowledge, this is the first study reporting accurate differentiation between several types of pancreatico-biliary tumors in a single molecular analytical procedure.

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Acknowledgments

This work was funded in part by EU FP6 grant LSHB-CT-2006-018771 (Integrated Project “MolDiag-Paca”), the German Federal Ministry of Education and Research (BMBF) within the framework of the Program of Medical Genome Research (PaCa-Net; project ID PKB-01GS08), Associazione Italiana Ricerca Cancro (AIRC, http://www.airc.it/), Fondazione CariParo (www.fondazionecariparo.it), and the Italian Ministry of Health, Rome, Italy (http://www.salute.gov.it/). The responsibility for the content lies exclusively with the authors.

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The authors declare that no conflicts of interest exist.

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Authors and Affiliations

  1. Division of Gastroenterology, University Hospital, Philipps-Universitaet Marburg, Marburg, Germany

    Thomas M. Gress, Lisa Fiedler & Malte Buchholz

  2. Internal Medicine I, University Hospital Ulm, Ulm, Germany

    Hans A. Kestler

  3. Research group of Bioinformatics and Systems Biology, Institute of Neural Information Processing, University of Ulm, Ulm, Germany

    Hans A. Kestler & Ludwig Lausser

  4. Institute of Pathology, University Hospital Tübingen, Tübingen, Germany

    Bence Sipos

  5. Department of Surgery, Technical University of Munich, Munich, Germany

    Christoph W. Michalski

  6. Department of Surgery, University of Heidelberg, Heidelberg, Germany

    Jens Werner & Nathalia Giese

  7. Department of Pathology, University of Verona, Verona, Italy

    Aldo Scarpa

  8. Klinik fuer Gastroenterologie, Endokrinologie, Stoffwechsel und Infektiologie, Fachbereich Medizin der Philipps-Universitaet Marburg, Baldinger Strasse, 35043, Marburg, Germany

    Thomas M. Gress

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  1. Thomas M. Gress
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  9. Aldo Scarpa
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Corresponding author

Correspondence to Thomas M. Gress.

Additional information

Thomas M. Gress and Hans A. Kestler contributed equally.

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Gress, T.M., Kestler, H.A., Lausser, L. et al. Differentiation of multiple types of pancreatico-biliary tumors by molecular analysis of clinical specimens. J Mol Med 90, 457–464 (2012). https://doi.org/10.1007/s00109-011-0832-5

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  • DOI: https://doi.org/10.1007/s00109-011-0832-5

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