A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

• Type of Material: Article
• Authors: Simeon Springer, Johns Hopkins University; Yuxuan Wang, Johns Hopkins University; Marco Dal Molin, Johns Hopkins University; David L. Masica, Johns Hopkins University; Yuchen Jiao, Johns Hopkins University; Isaac Kinde, Johns Hopkins University; Amanda Blackford, Johns Hopkins University; Siva P. Raman, Johns Hopkins University; Christopher L. Wolfgang, Johns Hopkins University; Tyler Tomita, Johns Hopkins University; Noushin Niknafs, Johns Hopkins University; Christopher Douville, Johns Hopkins University; Janine Ptak, Johns Hopkins University; Lisa Dobbyn, Johns Hopkins University; Peter J. Allen, Memorial Sloan-Kettering Cancer Center; David S. Klimstra, Memorial Sloan-Kettering Cancer Center; Mark A. Schattner, Memorial Sloan-Kettering Cancer Center; C. Max Schmidt, Indiana University; Michele Yip-Schneider, Indiana University; Oscar W. Cummings, Indiana University; Randall E. Brand, University of Pittsburgh; Herbert J. Zeh, University of Pittsburgh; Aatur D. Singhi, University of Pittsburgh; Aldo Scarpa, University and Hospital Trust of Verona; Roberto Salvia, University and Hospital Trust of Verona; Giuseppe Malleo, University and Hospital Trust of Verona; Giuseppe Zamboni, University and Hospital Trust of Verona; Massimo Falconi, IRCCS San Raffaele Scientific Institute; Jin-Young Jang, Seoul National University; Sun-Whe Kim, Seoul National University; Wooil Kwon, Seoul National University; Seung-Mo Hong, University of Ulsan; Ki-Byung Song, University of Ulsan; Song Cheol Kim, University of Ulsan; Niall Swan, St. Vincent’s University Hospital; Jean Murphy, St. Vincent’s University Hospital; Justin Geoghegan, St. Vincent’s University Hospital; William Brugge, Massachusetts General Hospital; Carlos Fernandez-Del Castillo, Massachusetts General Hospital; Mari Mino-Kenudson, Massachusetts General Hospital; Richard Schulick, University of Colorado; Barish H. Edil, University of Colorado; Nazmi Adsay, Emory University; Jorge Paulino, Hospital Curry Cabral; Jeanin van Hooft, Amsterdam Medical Center; Shinichi Yachida, National Cancer Center, Japan; Satoshi Nara, National Cancer Center, Japan; Nobuyoshi Hiraoka, National Cancer Center, Japan; Kenji Yamao, Aichi Cancer Center Hospital; Susuma Hijioka, Aichi Cancer Center Hospital; Schalk van der Merwe, Katholieke Universiteit Leuven; Michael Goggins, Johns Hopkins University; Marcia Irene Canto, Johns Hopkins University; Nita Ahuja, Johns Hopkins University; Kenzo Hirose, Johns Hopkins University; Martin Makary, Johns Hopkins University; Matthew J. Weiss, Johns Hopkins University; John Cameron, Johns Hopkins University; Meredith Pittman, Johns Hopkins University; James R. Eshleman, Johns Hopkins University; Luis A. Diaz, Johns Hopkins University; Nikolas Papadopoulos, Johns Hopkins University; Kenneth W. Kinzler, Johns Hopkins University; Rachel Karchin, Johns Hopkins University; Ralph H. Hruban, Johns Hopkins University; Bert Vogelstein, Johns Hopkins University; Anne Marie Lennon, Johns Hopkins University
• Language: English
• Date: 2015-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 AGA Institute.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1053/j.gastro.2015.07.041
• Title of Journal or Parent Work: Gastroenterology
• ISSN: 0016-5085
• Volume: 149
• Issue: 6
• Start Page: 1501
• End Page: 1510
• Grant/Funding Information: Supported by The Lustgarten Foundation for Pancreatic Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research, Susan Wojcicki and Dennis Troper, The Michael Rolfe Foundation, National Institutes of Health grant P50 CA62924, Associazione Italiana Ricerca Cancro (12182) Italian Ministry of Research (FIRB RBAP10AHJB) and Health (FIMP J33G13000210001).
• Keywords: Pancreatic Cyst; CANCER; PREVALENCE; UPDATED EXPERIENCE; Life Sciences & Biomedicine; MUTATIONS; GENES; IPMN; Diagnosis; CLINICOPATHOLOGICAL FEATURES; Molecular; Science & Technology; DNA; Gastroenterology & Hepatology; PAPILLARY MUCINOUS NEOPLASMS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology

Abstract

Background & Aims: The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients. Methods: We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid-pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53 and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers were compared with that of clinical markers, and a combination of molecular and clinical markers. Results: We identified molecular markers and clinical features that classified cyst type with 90%–100% sensitivity and 92%–98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery, and could therefore reduce the number of unnecessary operations by 91%. Conclusions: We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery.