1. A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts
- Author
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Volkan Adsay, Herbert J. Zeh, David S. Klimstra, Oscar W. Cummings, Jean Murphy, Bert Vogelstein, John L. Cameron, Jorge Paulino, Marco Dal Molin, Giuseppe Zamboni, Carlos Fernandez-del Castillo, Tyler M. Tomita, Song Cheol Kim, Michele T. Yip-Schneider, Nita Ahuja, Janine Ptak, Anne Marie Lennon, Siva P. Raman, C. Max Schmidt, Justin Geoghegan, Christopher L. Wolfgang, Kenji Yamao, Noushin Niknafs, Isaac Kinde, Mari Mino-Kenudson, Giuseppe Malleo, Jeanin E. van Hooft, Rachel Karchin, Kenneth W. Kinzler, Yuxuan Wang, Niall Swan, Seung-Mo Hong, James R. Eshleman, Christopher Douville, William R. Brugge, Lisa Dobbyn, Sun Whe Kim, Schalk Van der Merwe, Wooil Kwon, Mark A. Schattner, Matthew J. Weiss, Nickolas Papadopoulos, Barish H. Edil, Yuchen Jiao, Kenzo Hirose, Aldo Scarpa, Susuma Hijioka, Marcia I. Canto, Martin A. Makary, Shinichi Yachida, Roberto Salvia, Simeon Springer, Luis A. Diaz, Amanda L. Blackford, Aatur D. Singhi, David L. Masica, Nobuyoshi Hiraoka, Michael Goggins, Meredith E. Pittman, Satoshi Nara, Ki Byung Song, Randall E. Brand, Massimo Falconi, Peter J. Allen, Ralph H. Hruban, Jin-Young Jang, Richard D. Schulick, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, CCA -Cancer Center Amsterdam, Gastroenterology and Hepatology, Springer, Simeon, Wang, Yuxuan, Dal Molin, Marco, Masica David, L, Jiao, Yuchen, Kinde, Isaac, Blackford, Amanda, Raman Siva, P, Wolfgang Christopher, L, Tomita, Tyler, Niknafs, Noushin, Douville, Christopher, Ptak, Janine, Dobbyn, Lisa, Allen Peter, J, Klimstra David, S, Schattner Mark, A, Schmidt C., Max, Yip Schneider, Michele, Cummings Oscar, W, Brand Randall, E, Zeh Herbert, J, Singhi Aatur, D, Scarpa, Aldo, Salvia, Roberto, Malleo, Giuseppe, Zamboni, Giuseppe, Falconi, Massimo, Jang Jin, Young, Kim Sun, Whe, Kwon, Wooil, Hong Seung, Mo, Song Ki, Byung, Kim Song, Cheol, Swan, Niall, Murphy, Jean, Geoghegan, Justin, Brugge, William, Fernandez Del Castillo, Carlo, Mino Kenudson, Mari, Schulick, Richard, Edil Barish, H, Adsay, Volkan, Paulino, Jorge, van Hooft, Jeanin, Yachida, Shinichi, Nara, Satoshi, Hiraoka, Nobuyoshi, Yamao, Kenji, Hijioka, Susuma, van der Merwe, Schalk, Goggins, Michael, Canto Marcia, Irene, Ahuja, Nita, Hirose, Kenzo, Makary, Martin, Weiss Matthew, J, Cameron, John, Pittman, Meredith, Eshleman James, R, Diaz Luis A., Jr, Papadopoulos, Nickola, Kinzler Kenneth, W, Karchin, Rachel, Hruban Ralph, H, Vogelstein, Bert, and Lennon Anne, Marie
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,diagnosis ,medicine.disease_cause ,Article ,chemistry.chemical_compound ,Predictive Value of Tests ,CDKN2A ,Molecular marker ,Biomarkers, Tumor ,GNAS complex locus ,medicine ,Humans ,Genetic Predisposition to Disease ,Cyst ,molecular ,Genetic Testing ,Pancreas ,neoplasms ,IPMN ,pancreatic cyst ,Retrospective Studies ,Hepatology ,biology ,Intraductal papillary mucinous neoplasm ,Gastroenterology ,Middle Aged ,Prognosis ,medicine.disease ,Phenotype ,medicine.anatomical_structure ,chemistry ,Mutation ,biology.protein ,Female ,KRAS ,Pancreatic Cyst ,Pancreatic cysts ,Algorithms - 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 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.
- Published
- 2015