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Acinar cell carcinomas of the pancreas: a molecular analysis in a series of 57 cases

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Abstract

Pancreatic acinar cell carcinomas (PACs) are rare but are distinct aggressive neoplasms that phenotypically differ from pancreatic ductal adenocarcinomas (PDACs) and pancreatic neuroendocrine neoplasms (PNENs). Despite recent work on the genetic changes of PACs, their molecular pathogenesis is still poorly understood. In this study, we focus on a comparative genomic hybridization analysis. Based on frequent chromosomal imbalances, the involvement of DCC and c-MYC in the pathogenesis of PACs is further investigated. Moreover, we examine markers harboring potential therapeutic relevance (K-RAS, BRAF, EGFR, MGMT, HSP90, L1CAM, Her2). PACs revealed a microsatellite stable, chromosomal unstable genotype, defined by recurrent chromosomal losses of 1p, 3p, 4q, 5q, 6q, 8p, 9p, 11q, 13q, 16q, and 18, as well as gains of 1q, 7, 8q, 12, 17q, and 20q. Subsets of PAC displayed reduction/loss of DCC (79 %) and c-MYC-amplification (17 %). Significant EGFR expression occurred in 42 %, HSP90 expression in 98 %, L1CAM expression in 72 %, and loss of MGMT in 26 %. Two cases carried a K-RAS mutation. Mutations of EGFR or BRAF were not detected. All cases were Her2/neu-negative. PACs display characteristic chromosomal imbalances which are distinctly different from those in pancreatic ductal adenocarcinomas and pancreatic neuroendocrine neoplasms. Our findings suggest that DCC and c-MYC alterations may play an important role in the pathogenesis of PACs. Furthermore, EGFR, MGMT, HSP90, and L1CAM may be useful as therapeutic markers and predictors of response to therapy in a subset of PACs.

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Acknowledgments

The authors thank Regine Brandt, Maike Pacena, Anja Bredtmann, Andrea Müller, Stefanie Keller, and the NCT tissue bank Heidelberg for excellent technical support.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 224, D-69120, Heidelberg, Germany

    Frank Bergmann, Sebastian Aulmann, Matthias Kloor, Johannes Schweipert, Andreas Harjung, Philipp Mayer, David Capper, Esther Herpel, Anja Schleider, Peter Schirmacher, Gunhild Mechtersheimer & Hendrik Bläker

  2. Department of Pathology, University of Tübingen, Tübingen, Germany

    Bence Sipos

  3. Merck, Darmstadt, Darmstadt, Germany

    Anja von Heydebreck

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

    Werner Hartwig

  5. German Cancer Research Center, Heidelberg, Germany

    Gerhard Moldenhauer

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

    Gerhard Dyckhoff

  7. Department of Oral and Maxillofacial Surgery, University of Heidelberg, Heidelberg, Germany

    Kolja Freier

  8. Department of Pathology, Technical University Munich, Munich, Germany

    Günter Klöppel

  9. Institute of Pathology, University Hospital Charité Berlin, Berlin, Germany

    Hendrik Bläker

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  1. Frank Bergmann
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  2. Sebastian Aulmann
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Corresponding author

Correspondence to Frank Bergmann.

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Bergmann, F., Aulmann, S., Sipos, B. et al. Acinar cell carcinomas of the pancreas: a molecular analysis in a series of 57 cases. Virchows Arch 465, 661–672 (2014). https://doi.org/10.1007/s00428-014-1657-8

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  • DOI: https://doi.org/10.1007/s00428-014-1657-8

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