title: Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts.
abstract: OBJECTIVE
  Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear.
  
  
  METHODS
  GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst.
  
  
  RESULTS
  Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92).
  
  
  CONCLUSIONS
  The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.
authors.affiliation: Departments of Pathology, singhiad@upmc.edu.
authors.forename: Aatur D
authors.initials: AD
authors.lastname: Singhi
authors.affiliation: Departments of Pathology.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.affiliation: Medicine, and.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Fasanella
authors.affiliation: Medicine, and.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: McGrath
authors.affiliation: Departments of Pathology.
authors.forename: Reetesh K
authors.initials: RK
authors.lastname: Pai
authors.affiliation: Departments of Pathology.
authors.forename: N Paul
authors.initials: NP
authors.lastname: Ohori
authors.affiliation: Departments of Pathology.
authors.forename: Tanner L
authors.initials: TL
authors.lastname: Bartholow
authors.affiliation: Medicine, and.
authors.forename: Randall E
authors.initials: RE
authors.lastname: Brand
authors.affiliation: Medicine, and.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Chennat
authors.affiliation: Medicine, and.
authors.forename: Xuong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Medicine, and VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Georgios I
authors.initials: GI
authors.lastname: Papachristou
authors.affiliation: Medicine, and.
authors.forename: Adam
authors.initials: A
authors.lastname: Slivka
authors.affiliation: Surgery, the University of Pittsburgh Medical Center, and.
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.affiliation: Surgery, the University of Pittsburgh Medical Center, and.
authors.forename: Amer H
authors.initials: AH
authors.lastname: Zureikat
authors.affiliation: Surgery, the University of Pittsburgh Medical Center, and.
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Surgery, the University of Pittsburgh Medical Center, and.
authors.forename: Allan
authors.initials: A
authors.lastname: Tsung
authors.affiliation: Departments of Pathology.
authors.forename: Geeta S
authors.initials: GS
authors.lastname: Mantha
authors.affiliation: Medicine, and VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
authors.forename: Asif
authors.initials: A
authors.lastname: Khalid
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics; D002864:Chromogranins; D020420:Cyst Fluid / Q000737:chemistry / Q000378:metabolism; D018293:Cystadenoma, Serous / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D010181:Pancreatic Cyst / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics; D011300:Preoperative Care; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D002864:Chromogranins; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins