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

Simeon Springer, Yuxuan Wang, Marco Dal Molin, David L. Masica, Yuchen Jiao, Isaac Kinde, Amanda Blackford, Siva P. Raman, Christopher L. Wolfgang, Tyler Tomita, Noushin Niknafs, Christopher Douville, Janine Ptak, Lisa Dobbyn, Peter J. Allen, David S. Klimstra, Mark A. Schattner, C. Max Schmidt, Michele Yip-Schneider, Oscar W. CummingsRandall E. Brand, Herbert J. Zeh, Aatur D. Singhi, Aldo Scarpa, Roberto Salvia, Giuseppe Malleo, Giuseppe Zamboni, Massimo Falconi, Jin Young Jang, Sun Whe Kim, Wooil Kwon, Seung Mo Hong, Ki Byung Song, Song Cheol Kim, Niall Swan, Jean Murphy, Justin Geoghegan, William Brugge, Carlos Fernandez-Del Castillo, Mari Mino-Kenudson, Richard Schulick, Barish H. Edil, Volkan Adsay, Jorge Paulino, Jeanin Van Hooft, Shinichi Yachida, Satoshi Nara, Nobuyoshi Hiraoka, Kenji Yamao, Susuma Hijioka, Schalk Van Der Merwe, Michael Goggins, Marcia Irene Canto, Nita Ahuja, Kenzo Hirose, Martin Makary, Matthew J. Weiss, John Cameron, Meredith Pittman, James R. Eshleman, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Rachel Karchin, Ralph H. Hruban, Bert Vogelstein, Anne Marie Lennon

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

Background and 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 was 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.

Original languageEnglish (US)
Pages (from-to)1501-1510
Number of pages10
JournalGastroenterology
Volume149
Issue number6
DOIs
StatePublished - Nov 2015
Externally publishedYes

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Keywords

  • Diagnosis
  • IPMN
  • Molecular
  • Pancreatic Cyst

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Springer, S., Wang, Y., Dal Molin, M., Masica, D. L., Jiao, Y., Kinde, I., Blackford, A., Raman, S. P., Wolfgang, C. L., Tomita, T., Niknafs, N., Douville, C., Ptak, J., Dobbyn, L., Allen, P. J., Klimstra, D. S., Schattner, M. A., Schmidt, C. M., Yip-Schneider, M., ... Lennon, A. M. (2015). A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts. Gastroenterology, 149(6), 1501-1510. https://doi.org/10.1053/j.gastro.2015.07.041