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GNAS but Not Extended RAS Mutations Spectrum are Associated with a Better Prognosis in Intraductal Pancreatic Mucinous Neoplasms

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The management of intraductal papillary mucinous neoplasms (IPMNs) is mainly based on imaging features and clinical symptoms, and remains challenging.

Objective

The aim of this study was to assess GNAS, RAS family (KRAS, NRAS and HRAS), BRAF, and PIK3CA mutation status in resected IPMNs and correlate it with clinicopathological characteristics and patient survival.

Methods

Overall, 149 consecutive unselected patients who underwent pancreatectomy for IPMNs were included. After dissection from formalin-fixed and paraffin-embedded tumors, GNAS mutational screening was assessed by allelic discrimination using Taqman® probes and confirmed by SNaPshot analysis. RAS family, BRAF, and PIK3CA mutational screening was assessed by high resolution melt and Sanger sequencing.

Results

Gastric- and intestinal-type IPMNs were the most frequent lesions (52% and 41%, respectively). Intestinal-type IPMNs were more frequently associated high-grade dysplasia (49%) and were the only IPMNs associated with colloid-type carcinoma. All pancreatobiliary IPMNs were invasive lesions, located in the main pancreatic duct. GNAS-activating mutations were strongly associated with the intestinal phenotype (p < 10−4), while RAS pathway mutations were not associated with any particular phenotype. Mutations within other members of the epidermal growth factor receptor (EGFR) pathway were very rare (2%). GNAS-mutated IPMNs were rarely invasive (11%) and almost exclusively (83%) of the colloid type. For invasive lesions, multivariate analyses determined that only node negativity was associated with improved cancer-specific survival, but, in univariate analysis, GNAS mutation was associated with prolonged survival.

Conclusion

In patients selected for surgery, GNAS mutation analysis and tumor phenotype can help to better predict patient prognosis. In the near future, a more precise mutational analysis of IPMNs might help to better tailor their management.

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Acknowledgment

The authors would like to thank Walid Chemlali for technical assistance, and all the Beaujon and Cochin clinical and technical staff for their helpful discussions.

Author information

Authors and Affiliations

  1. Department of Hepato-Pancreato-Biliary Surgery – Pôle des Maladies de l’Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France

    Sébastien Gaujoux MD, PhD, Alina Parvanescu MD, Manuella Cesaretti MD & Alain Sauvanet MD

  2. Université Paris Descartes, Paris, France

    Sébastien Gaujoux MD, PhD

  3. INSERM U1016, CNRS UMR8104, Institut Cochin, Paris, France

    Sébastien Gaujoux MD, PhD

  4. Institut National de la Santé et de la Recherche Médicale – Centre de Recherche Biomédicale Bichat Beaujon (CRI)/INSERM U1149, Clichy, France

    Alina Parvanescu MD, Vinciane Rebours MD, PhD, Philippe Lévy MD & Jérôme Cros MD, PhD

  5. Institut National de la Santé et de la Recherche Médicale-U986, Groupe Hospitalier Paris-Sud, Le Kremlin-Bicêtre, France

    Caroline Silve MD

  6. Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Paris, France

    Caroline Silve MD

  7. Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore/Filière OSCAR, Le Kremlin-Bicêtre, France

    Caroline Silve MD

  8. Unité de Pharmagogénomique, Institut Curie, Paris, France

    Ivan Bieche MD, PhD

  9. Department of Pancreatology-Gastroenterology, Pôle des Maladies de l’Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France

    Vinciane Rebours MD, PhD & Philippe Lévy MD

  10. Université Paris Diderot, Paris, France

    Vinciane Rebours MD, PhD, Philippe Lévy MD, Alain Sauvanet MD & Jérôme Cros MD, PhD

  11. Department of Pathology, AP-HP, Hôpital Beaujon, Clichy, France

    Jérôme Cros MD, PhD

Authors
  1. Sébastien Gaujoux MD, PhD
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  2. Alina Parvanescu MD
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  3. Manuella Cesaretti MD
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  4. Caroline Silve MD
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  5. Ivan Bieche MD, PhD
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  6. Vinciane Rebours MD, PhD
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  7. Philippe Lévy MD
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  8. Alain Sauvanet MD
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  9. Jérôme Cros MD, PhD
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Corresponding author

Correspondence to Sébastien Gaujoux MD, PhD.

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Disclosures

Sébastien Gaujoux, Alina Parvanescu, Manuella Cesaretti, Caroline Silve, Ivan Bieche, Vinciane Rebours, Philippe Lévy, Alain Sauvanet, and Jérôme Cros have no financial or personal conflicts of interest in relation to this study.

Funding

This work was supported by Fonds d’Aide à la Recherche et à l’Evaluation (FARE) from the Société Nationale Française de Gastro-entérologie (SNFGE).

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Gaujoux, S., Parvanescu, A., Cesaretti, M. et al. GNAS but Not Extended RAS Mutations Spectrum are Associated with a Better Prognosis in Intraductal Pancreatic Mucinous Neoplasms. Ann Surg Oncol 26, 2640–2650 (2019). https://doi.org/10.1245/s10434-019-07389-6

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  • DOI: https://doi.org/10.1245/s10434-019-07389-6

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