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


Journal

Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840

Informations de publication

Date de publication:
Aug 2019
Historique:
received: 02 01 2019
pubmed: 27 4 2019
medline: 19 12 2019
entrez: 27 4 2019
Statut: ppublish

Résumé

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

Sections du résumé

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

Identifiants

pubmed: 31025231
doi: 10.1245/s10434-019-07389-6
pii: 10.1245/s10434-019-07389-6
doi:

Substances chimiques

Biomarkers, Tumor 0
Chromogranins 0
GNAS protein, human EC 3.6.1.-
GTP-Binding Protein alpha Subunits, Gs EC 3.6.5.1
ras Proteins EC 3.6.5.2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2640-2650

Auteurs

Sébastien Gaujoux (S)

Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France. sebastien.gaujoux@aphp.fr.
Université Paris Descartes, Paris, France. sebastien.gaujoux@aphp.fr.
INSERM U1016, CNRS UMR8104, Institut Cochin, Paris, France. sebastien.gaujoux@aphp.fr.

Alina Parvanescu (A)

Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France.
Institut National de la Santé et de la Recherche Médicale - Centre de Recherche Biomédicale Bichat Beaujon (CRI)/INSERM U1149, Clichy, France.

Manuella Cesaretti (M)

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

Caroline Silve (C)

Institut National de la Santé et de la Recherche Médicale-U986, Groupe Hospitalier Paris-Sud, Le Kremlin-Bicêtre, France.
Service de Génétique et Biologie Moléculaires, Hôpital Cochin, Paris, France.
Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore/Filière OSCAR, Le Kremlin-Bicêtre, France.

Ivan Bieche (I)

Unité de Pharmagogénomique, Institut Curie, Paris, France.

Vinciane Rebours (V)

Institut National de la Santé et de la Recherche Médicale - Centre de Recherche Biomédicale Bichat Beaujon (CRI)/INSERM U1149, Clichy, France.
Department of Pancreatology-Gastroenterology, Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France.
Université Paris Diderot, Paris, France.

Philippe Lévy (P)

Institut National de la Santé et de la Recherche Médicale - Centre de Recherche Biomédicale Bichat Beaujon (CRI)/INSERM U1149, Clichy, France.
Department of Pancreatology-Gastroenterology, Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France.
Université Paris Diderot, Paris, France.

Alain Sauvanet (A)

Department of Hepato-Pancreato-Biliary Surgery - Pôle des Maladies de l'Appareil Digestif (PMAD), AP-HP, Hôpital Beaujon, Clichy, France.
Université Paris Diderot, Paris, France.

Jérôme Cros (J)

Institut National de la Santé et de la Recherche Médicale - Centre de Recherche Biomédicale Bichat Beaujon (CRI)/INSERM U1149, Clichy, France.
Université Paris Diderot, Paris, France.
Department of Pathology, AP-HP, Hôpital Beaujon, Clichy, France.

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Classifications MeSH