Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Issue 12 (28th September 2017)

• Record Type: Journal Article
• Authors: Singhi, Aatur D; McGrath, Kevin; Brand, Randall E; Khalid, Asif; Zeh, Herbert J; Chennat, Jennifer S; Fasanella, Kenneth E; Papachristou, Georgios I; Slivka, Adam; Bartlett, David L; Dasyam, Anil K; Hogg, Melissa; Lee, Kenneth K; Marsh, James Wallis; Monaco, Sara E; Ohori, N Paul; Pingpank, James F; Tsung, Allan; Zureikat, Amer H; Wald, Abigail I; Nikiforova, Marina N
• Is Part Of: Gut. Volume 67:Issue 12(2018)
• Page Start: 2131
• Page End: 2141
• Publication Date: 2017-09-28
• Subjects: pancreatic cancer -- pancreatic pathology -- pancreatic epidemiology -- pancreato-biliary disorders; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2016-313586
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: DNA-based testing of pancreatic cyst fluid (PCF) is a useful adjunct to the evaluation of pancreatic cysts (PCs). Mutations in KRAS / GNAS are highly specific for intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), while TP53 / PIK3CA / PTEN alterations are associated with advanced neoplasia. A prospective study was performed to evaluate preoperative PCF DNA testing. Design: Over 43-months, 626 PCF specimens from 595 patients were obtained by endoscopic ultrasound (EUS)-fine needle aspiration and assessed by targeted next-generation sequencing (NGS). Molecular results were correlated with EUS findings, ancillary studies and follow-up. A separate cohort of 159 PCF specimens was also evaluated for KRAS / GNAS mutations by Sanger sequencing. Results: KRAS/GNAS mutations were identified in 308 (49%) PCs, while alterations in TP53/PIK3CA/PTEN were present in 35 (6%) cases. Based on 102 (17%) patients with surgical follow-up, KRAS/GNAS mutations were detected in 56 (100%) IPMNs and 3 (30%) MCNs, and associated with 89% sensitivity and 100% specificity for a mucinous PC. In comparison, KRAS/GNAS mutations by Sanger sequencing had a 65% sensitivity and 100% specificity. By NGS, the combination of KRAS/GNAS mutations and alterations in TP53/PIK3CA/PTEN had an 89% sensitivity and 100% specificity for advanced neoplasia. Ductal dilatation, a mural nodule and malignant cytopathology had lower sensitivities (42%, 32% and 32%, respectively) and specificities (74%, 94% and 98%, respectively). Conclusions: In contrast to Sanger sequencing, preoperative NGS of PCF for KRAS / GNAS mutations is highly sensitive for IPMNs and specific for mucinous PCs. In addition, the combination of TP53 / PIK3CA / PTEN alterations is a useful preoperative marker for advanced neoplasia.