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Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia.
Gut 2018; 67(12):2131-2141Gut

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.

Authors+Show Affiliations

Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.Department of Pathology, University of Pittsburgh Medical Center Health System, Pittsburgh, Pennsylvania, USA.

Pub Type(s)

Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28970292

Citation

Singhi, Aatur D., et al. "Preoperative Next-generation Sequencing of Pancreatic Cyst Fluid Is Highly Accurate in Cyst Classification and Detection of Advanced Neoplasia." Gut, vol. 67, no. 12, 2018, pp. 2131-2141.
Singhi AD, McGrath K, Brand RE, et al. Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut. 2018;67(12):2131-2141.
Singhi, A. D., McGrath, K., Brand, R. E., Khalid, A., Zeh, H. J., Chennat, J. S., ... Nikiforova, M. N. (2018). Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut, 67(12), pp. 2131-2141. doi:10.1136/gutjnl-2016-313586.
Singhi AD, et al. Preoperative Next-generation Sequencing of Pancreatic Cyst Fluid Is Highly Accurate in Cyst Classification and Detection of Advanced Neoplasia. Gut. 2018;67(12):2131-2141. PubMed PMID: 28970292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. AU - Singhi,Aatur D, AU - McGrath,Kevin, AU - Brand,Randall E, AU - Khalid,Asif, AU - Zeh,Herbert J, AU - Chennat,Jennifer S, AU - Fasanella,Kenneth E, AU - Papachristou,Georgios I, AU - Slivka,Adam, AU - Bartlett,David L, AU - Dasyam,Anil K, AU - Hogg,Melissa, AU - Lee,Kenneth K, AU - Marsh,James Wallis, AU - Monaco,Sara E, AU - Ohori,N Paul, AU - Pingpank,James F, AU - Tsung,Allan, AU - Zureikat,Amer H, AU - Wald,Abigail I, AU - Nikiforova,Marina N, Y1 - 2017/09/28/ PY - 2016/12/13/received PY - 2017/08/29/revised PY - 2017/09/14/accepted PY - 2017/10/4/pubmed PY - 2018/11/27/medline PY - 2017/10/4/entrez KW - pancreatic cancer KW - pancreatic epidemiology KW - pancreatic pathology KW - pancreato-biliary disorders SP - 2131 EP - 2141 JF - Gut JO - Gut VL - 67 IS - 12 N2 - 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. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/28970292/Preoperative_next_generation_sequencing_of_pancreatic_cyst_fluid_is_highly_accurate_in_cyst_classification_and_detection_of_advanced_neoplasia_ L2 - http://gut.bmj.com/cgi/pmidlookup?view=long&pmid=28970292 DB - PRIME DP - Unbound Medicine ER -