Endoscopic ultrasound-guided fine-needle aspiration plus KRAS and GNAS mutation in malignant intraductal papillary mucinous neoplasm of the pancreas

Barbara Bournet; Alix Vignolle-Vidoni; David Grand; Céline Roques; Florence Breibach; Jérome Cros; Fabrice Muscari; Nicolas Carrère; Janick Selves; Pierre Cordelier; Louis Buscail

doi:10.1055/s-0042-117216

Endoscopic ultrasound-guided fine-needle aspiration plus KRAS and GNAS mutation in malignant intraductal papillary mucinous neoplasm of the pancreas

Endosc Int Open. 2016 Dec;4(12):E1228-E1235. doi: 10.1055/s-0042-117216. Epub 2016 Nov 10.

Authors

Affiliations

¹ Department of Gastroenterology and INSERM UMR 1037, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France; INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France.
² INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France.
³ Department of Pathology, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France.
⁴ Department of Pathology, Beaujon Hospital, University of Paris Diderot, Clichy, France.
⁵ Department of Digestive Surgery, CHU Toulouse Rangueil, University of Toulouse, Toulouse, France.
⁶ INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France; Department of Digestive Surgery, CHU Toulouse Purpan, University of Toulouse, Toulouse, France.
⁷ INSERM UMR 1037, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France; Department of Pathology, University Institute of Cancer of Toulouse, University of Toulouse, Toulouse, France.

Abstract

Background:KRAS and GNAS mutations are common in intraductal papillary mucinous neoplasia of the pancreas (IPMN). The aims of this study were to assess the role of pre-therapeutic cytopathology combined with KRAS and GNAS mutation assays within cystic fluid sampled by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) to predict malignancy of IPMN. Patients and methods: We prospectively included 37 IPMN patients with clinical and/or imaging predictors of malignancy (men: 24; mean age: 69.5 years). Cytopathology (performed on cystic fluid and/or IPMN nodules), KRAS (Exon 2, codon 12) and GNAS (Exon 8, codon 201) mutations assays (using TaqMan^® allelic discrimination) were performed on EUS-FNA material. The final diagnosis was obtained from IPMN resections (n = 18); surgical biopsies, EUS-FNA analyses, and follow-up (n = 19): 10 and 27 IPMN were benign and malignant, respectively. Results: Sensitivity, specificity, positive and negative predictive values, and accuracy of cytopathology alone to diagnose IPMN malignancy were 55 %, 100 %, 100 %, 45 %, and 66 %, respectively. When KRAS-mutation analysis was combined with cytopathology these values were 92 %, 50 %, 83 %, 71 %, and 81 %, respectively. GNAS assays did not improve the performances of cytopathology alone or those of cytopathology plus a KRAS assay. Conclusions: In patients with a likelihood of malignant IPMN at pre-therapeutic investigation, testing for KRAS mutations in cystic fluid sampling by EUS-FNA improved the results of cytopathology for the diagnosis of malignancy whereas GNAS mutation assay did not.