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Clinicopathological Correlates of Activating GNAS Mutations in Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Intraductal papillary mucinous neoplasms (IPMNs) are the most common cystic precursor lesions of invasive pancreatic cancer. The recent identification of activating GNAS mutations at codon 201 in IPMNs is a promising target for early detection and therapy. The purpose of this study was to explore clinicopathological correlates of GNAS mutational status in resected IPMNs.

Methods

Clinical and pathologic characteristics were retrieved on 54 patients in whom GNAS codon 201 mutational status was previously reported (“historical group”, Wu et al. Sci Transl Med 3:92ra66, 2011). In addition, a separate cohort of 32 patients (validation group) was included. After microdissection and DNA extraction, GNAS status was determined in the validation group by pyrosequencing.

Results

GNAS activating mutations were found in 64 % of the 32 IPMNs included in the validation group, compared with a previously reported prevalence of 57 % in the historical group. Overall, 52 of 86 (61 %) of IPMNs demonstrated GNAS mutations in the two studies combined. Analysis of both groups confirmed that demographic characteristics, tumor location, ductal system involvement, focality, size, grade of dysplasia, presence of an associated cancer, and overall survival were not correlated with GNAS mutational status. Stratified by histological subtype, 100 % of intestinal type IPMNs demonstrated GNAS mutations compared to 51 % of gastric IPMN, 71 % of pancreatobiliary IPMNs, and 0 % of oncocytic IPMNs.

Conclusions

GNAS activating mutations can be reliably detected in IPMNs by pyrosequencing. In terms of clinicopathological parameters, only histological subtype was correlated with mutational frequency, with the intestinal phenotype always associated with GNAS mutations.

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Acknowledgment

The authors thank Michael Rolfe and the Lustgarten Foundations for their support.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Marco Dal Molin MD, Hanno Matthaei MD, Marija Debeljak B.S., Michael G. Goggins MD, James R. Eshleman MD, PhD, Ralph H. Hruban MD & Anirban Maitra MBBS

  2. Unit of General Surgery B, Pancreas Institute, Department of Surgery, “G.B. Rossi” Hospital, University of Verona Hospital Trust, Verona, Italy

    Marco Dal Molin MD, Giovanni Butturini MD, PhD, Roberto Salvia MD, PhD & Claudio Bassi MD

  3. Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany

    Hanno Matthaei MD

  4. Ludwig Center for Cancer Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jian Wu PhD, Kenneth W. Kinzler PhD & Bert Vogelstein MD

  5. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jian Wu PhD, Kenneth W. Kinzler PhD & Bert Vogelstein MD

  6. Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Amanda Blackford Sc.M., Neda Rezaee MD, Christopher L. Wolfgang MD, PhD & Ralph H. Hruban MD

  7. Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Christopher L. Wolfgang MD, PhD, Michael G. Goggins MD, James R. Eshleman MD, PhD, Ralph H. Hruban MD & Anirban Maitra MBBS

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  1. Marco Dal Molin MD
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  2. Hanno Matthaei MD
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  3. Jian Wu PhD
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  4. Amanda Blackford Sc.M.
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  5. Marija Debeljak B.S.
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  6. Neda Rezaee MD
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  7. Christopher L. Wolfgang MD, PhD
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  8. Giovanni Butturini MD, PhD
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  9. Roberto Salvia MD, PhD
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  10. Claudio Bassi MD
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  11. Michael G. Goggins MD
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  12. Kenneth W. Kinzler PhD
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  13. Bert Vogelstein MD
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  14. James R. Eshleman MD, PhD
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  15. Ralph H. Hruban MD
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  16. Anirban Maitra MBBS
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Corresponding author

Correspondence to Anirban Maitra MBBS.

Additional information

Marco Dal Molin and Hanno Matthaei contributed equally to this article, and both should be considered first author.

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Dal Molin, M., Matthaei, H., Wu, J. et al. Clinicopathological Correlates of Activating GNAS Mutations in Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas. Ann Surg Oncol 20, 3802–3808 (2013). https://doi.org/10.1245/s10434-013-3096-1

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  • DOI: https://doi.org/10.1245/s10434-013-3096-1

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