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

168 Citations (Scopus)

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

Fingerprint

Pancreatic Cyst
Biomarkers
Cysts
Pancreatic Neoplasms
Neoplasms
Serous Cystadenoma
Cyst Fluid
High-Throughput Nucleotide Sequencing
Aneuploidy
Retrospective Studies
Technology
Physicians
Mutation
Genes

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., ... 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

A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts. / 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, Carlos; 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.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Karchin, Rachel; Hruban, Ralph H.; Vogelstein, Bert; Lennon, Anne Marie.

In: Gastroenterology, Vol. 149, No. 6, 11.2015, p. 1501-1510.

Research output: Contribution to journalArticle

Springer, S, Wang, Y, Dal Molin, M, Masica, DL, Jiao, Y, Kinde, I, Blackford, A, Raman, SP, Wolfgang, CL, Tomita, T, Niknafs, N, Douville, C, Ptak, J, Dobbyn, L, Allen, PJ, Klimstra, DS, Schattner, MA, Schmidt, CM, Yip-Schneider, M, Cummings, OW, Brand, RE, Zeh, HJ, Singhi, AD, Scarpa, A, Salvia, R, Malleo, G, Zamboni, G, Falconi, M, Jang, JY, Kim, SW, Kwon, W, Hong, SM, Song, KB, Kim, SC, Swan, N, Murphy, J, Geoghegan, J, Brugge, W, Fernandez-Del Castillo, C, Mino-Kenudson, M, Schulick, R, Edil, BH, Adsay, V, Paulino, J, Van Hooft, J, Yachida, S, Nara, S, Hiraoka, N, Yamao, K, Hijioka, S, Van Der Merwe, S, Goggins, M, Canto, MI, Ahuja, N, Hirose, K, Makary, M, Weiss, MJ, Cameron, J, Pittman, M, Eshleman, JR, Diaz, LA, Papadopoulos, N, Kinzler, KW, Karchin, R, Hruban, RH, Vogelstein, B & Lennon, AM 2015, 'A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts', Gastroenterology, vol. 149, no. 6, pp. 1501-1510. https://doi.org/10.1053/j.gastro.2015.07.041
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, Carlos ; 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. ; Papadopoulos, Nickolas ; Kinzler, Kenneth W. ; Karchin, Rachel ; Hruban, Ralph H. ; Vogelstein, Bert ; Lennon, Anne Marie. / A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts. In: Gastroenterology. 2015 ; Vol. 149, No. 6. pp. 1501-1510.
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TY - JOUR

T1 - A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts

AU - Springer, Simeon

AU - Wang, Yuxuan

AU - Dal Molin, Marco

AU - Masica, David L.

AU - Jiao, Yuchen

AU - Kinde, Isaac

AU - Blackford, Amanda

AU - Raman, Siva P.

AU - Wolfgang, Christopher L.

AU - Tomita, Tyler

AU - Niknafs, Noushin

AU - Douville, Christopher

AU - Ptak, Janine

AU - Dobbyn, Lisa

AU - Allen, Peter J.

AU - Klimstra, David S.

AU - Schattner, Mark A.

AU - Schmidt, C. Max

AU - Yip-Schneider, Michele

AU - Cummings, Oscar W.

AU - Brand, Randall E.

AU - Zeh, Herbert J.

AU - Singhi, Aatur D.

AU - Scarpa, Aldo

AU - Salvia, Roberto

AU - Malleo, Giuseppe

AU - Zamboni, Giuseppe

AU - Falconi, Massimo

AU - Jang, Jin Young

AU - Kim, Sun Whe

AU - Kwon, Wooil

AU - Hong, Seung Mo

AU - Song, Ki Byung

AU - Kim, Song Cheol

AU - Swan, Niall

AU - Murphy, Jean

AU - Geoghegan, Justin

AU - Brugge, William

AU - Fernandez-Del Castillo, Carlos

AU - Mino-Kenudson, Mari

AU - Schulick, Richard

AU - Edil, Barish H.

AU - Adsay, Volkan

AU - Paulino, Jorge

AU - Van Hooft, Jeanin

AU - Yachida, Shinichi

AU - Nara, Satoshi

AU - Hiraoka, Nobuyoshi

AU - Yamao, Kenji

AU - Hijioka, Susuma

AU - Van Der Merwe, Schalk

AU - Goggins, Michael

AU - Canto, Marcia Irene

AU - Ahuja, Nita

AU - Hirose, Kenzo

AU - Makary, Martin

AU - Weiss, Matthew J.

AU - Cameron, John

AU - Pittman, Meredith

AU - Eshleman, James R.

AU - Diaz, Luis A.

AU - Papadopoulos, Nickolas

AU - Kinzler, Kenneth W.

AU - Karchin, Rachel

AU - Hruban, Ralph H.

AU - Vogelstein, Bert

AU - Lennon, Anne Marie

PY - 2015/11

Y1 - 2015/11

N2 - 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.

AB - 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.

KW - Diagnosis

KW - IPMN

KW - Molecular

KW - Pancreatic Cyst

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