Multicenter Study

. 2015 Nov;149(6):1501-10.

doi: 10.1053/j.gastro.2015.07.041. Epub 2015 Aug 4.

A combination of molecular markers and clinical features improve the classification of pancreatic cysts

Simeon Springer¹, Yuxuan Wang¹, Marco Dal Molin², David L Masica³, Yuchen Jiao¹, Isaac Kinde¹, Amanda Blackford⁴, Siva P Raman⁵, Christopher L Wolfgang⁶, Tyler Tomita⁷, Noushin Niknafs⁷, Christopher Douville⁷, Janine Ptak¹, Lisa Dobbyn¹, Peter J Allen⁸, David S Klimstra⁹, Mark A Schattner¹⁰, C Max Schmidt¹¹, Michele Yip-Schneider¹², Oscar W Cummings¹², Randall E Brand¹³, Herbert J Zeh¹⁴, Aatur D Singhi¹⁵, Aldo Scarpa¹⁶, Roberto Salvia¹⁷, Giuseppe Malleo¹⁷, Giuseppe Zamboni¹⁸, Massimo Falconi¹⁹, Jin-Young Jang²⁰, Sun-Whe Kim²⁰, Wooil Kwon²⁰, Seung-Mo Hong²¹, Ki-Byung Song²², Song Cheol Kim²², Niall Swan²³, Jean Murphy²³, Justin Geoghegan²⁴, William Brugge²⁵, Carlos Fernandez-Del Castillo²⁶, Mari Mino-Kenudson²⁷, Richard Schulick²⁸, Barish H Edil²⁸, Volkan Adsay²⁹, Jorge Paulino³⁰, Jeanin van Hooft³¹, Shinichi Yachida³², Satoshi Nara³², Nobuyoshi Hiraoka³², Kenji Yamao³³, Susuma Hijioka³³, Schalk van der Merwe³⁴, Michael Goggins³⁵, Marcia Irene Canto³⁶, Nita Ahuja³⁷, Kenzo Hirose³⁷, Martin Makary³⁷, Matthew J Weiss³⁷, John Cameron³⁷, Meredith Pittman², James R Eshleman¹, Luis A Diaz Jr³⁸, Nickolas Papadopoulos¹, Kenneth W Kinzler¹, Rachel Karchin³⁹, Ralph H Hruban⁴⁰, Bert Vogelstein¹, Anne Marie Lennon⁴¹

Affiliations

¹ The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
² The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University, Baltimore, Maryland.
³ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
⁴ Department of Biostatistics and Bioinformatics, The Johns Hopkins University, Baltimore, Maryland.
⁵ Department of Radiology, The Johns Hopkins University, Baltimore, Maryland.
⁶ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
⁷ Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
⁹ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹⁰ Department of Gastroenterology, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹¹ Department of Surgery, University of Indiana, Bloomington, Indiana.
¹² Department of Pathology, University of Indiana, Bloomington, Indiana.
¹³ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹⁴ Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹⁵ Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹⁶ ARC-Net Research Centre, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology, General Surgery B, University and Hospital Trust of Verona, Verona, Italy.
¹⁷ Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
¹⁸ Department of Pathology, General Surgery B, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology, Ospedale Sacro Cuore-Don Calabraia, Negrar, Italy.
¹⁹ Division of Pancreatic Surgery, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²⁰ Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
²¹ Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²² Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²³ Department of Histopathology, St Vincent's University Hospital, Dublin, Ireland.
²⁴ Department of Surgery, St Vincent's University Hospital, Dublin, Ireland.
²⁵ Department of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
²⁶ Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
²⁷ Department of Histopathology, Massachusetts General Hospital, Boston, Massachusetts.
²⁸ Department of Surgery, University of Colorado, Boulder, Colorado.
²⁹ Department of Pathology, Emory University, Atlanta, Georgia.
³⁰ Department of Pathology, Centro Hepatobiliopancreático e Transplantação, Hospital Curry Cabral, Lisbon, Portugal.
³¹ Department of Gastroenterology and Hepatology, Amsterdam Medical Center, The Netherlands.
³² Department of Hepatobiliary and Pancreatic Surgery, Pathology and Cancer Genomics, National Cancer Center Hospital and National Cancer Center Research Institute, Tokyo, Japan.
³³ Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
³⁴ Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
³⁵ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
³⁶ Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
³⁷ Department of Surgery, The Johns Hopkins University, Baltimore, Maryland.
³⁸ The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland.
³⁹ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
⁴⁰ The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
⁴¹ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University, Baltimore, Maryland. Electronic address: amlennon@jhmi.edu.

PMID: 26253305
PMCID: PMC4782782
DOI: 10.1053/j.gastro.2015.07.041

Multicenter Study

A combination of molecular markers and clinical features improve the classification of pancreatic cysts

Simeon Springer et al. Gastroenterology. 2015 Nov.

. 2015 Nov;149(6):1501-10.

doi: 10.1053/j.gastro.2015.07.041. Epub 2015 Aug 4.

Authors

Affiliations

¹ The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland.
² The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University, Baltimore, Maryland.
³ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
⁴ Department of Biostatistics and Bioinformatics, The Johns Hopkins University, Baltimore, Maryland.
⁵ Department of Radiology, The Johns Hopkins University, Baltimore, Maryland.
⁶ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
⁷ Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland.
⁸ Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
⁹ Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹⁰ Department of Gastroenterology, Memorial Sloan-Kettering Cancer Center, New York, New York.
¹¹ Department of Surgery, University of Indiana, Bloomington, Indiana.
¹² Department of Pathology, University of Indiana, Bloomington, Indiana.
¹³ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹⁴ Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹⁵ Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹⁶ ARC-Net Research Centre, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology, General Surgery B, University and Hospital Trust of Verona, Verona, Italy.
¹⁷ Department of Surgery, University and Hospital Trust of Verona, Verona, Italy.
¹⁸ Department of Pathology, General Surgery B, University and Hospital Trust of Verona, Verona, Italy; Department of Pathology, Ospedale Sacro Cuore-Don Calabraia, Negrar, Italy.
¹⁹ Division of Pancreatic Surgery, Department of Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy.
²⁰ Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
²¹ Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²² Department of Hepatobiliary and Pancreas Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²³ Department of Histopathology, St Vincent's University Hospital, Dublin, Ireland.
²⁴ Department of Surgery, St Vincent's University Hospital, Dublin, Ireland.
²⁵ Department of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
²⁶ Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
²⁷ Department of Histopathology, Massachusetts General Hospital, Boston, Massachusetts.
²⁸ Department of Surgery, University of Colorado, Boulder, Colorado.
²⁹ Department of Pathology, Emory University, Atlanta, Georgia.
³⁰ Department of Pathology, Centro Hepatobiliopancreático e Transplantação, Hospital Curry Cabral, Lisbon, Portugal.
³¹ Department of Gastroenterology and Hepatology, Amsterdam Medical Center, The Netherlands.
³² Department of Hepatobiliary and Pancreatic Surgery, Pathology and Cancer Genomics, National Cancer Center Hospital and National Cancer Center Research Institute, Tokyo, Japan.
³³ Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, Japan.
³⁴ Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
³⁵ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
³⁶ Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
³⁷ Department of Surgery, The Johns Hopkins University, Baltimore, Maryland.
³⁸ The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland.
³⁹ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland; The Johns Hopkins Medical Institutions and the Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
⁴⁰ The Ludwig Center and Howard Hughes Medical Institute at the Sidney Kimmel Cancer Center, The Johns Hopkins University, Baltimore, Maryland; The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Pathology, The Johns Hopkins University, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.
⁴¹ The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, Maryland; Department of Surgery, The Johns Hopkins University, Baltimore, Maryland; Department of Medicine, The Johns Hopkins University, Baltimore, Maryland. Electronic address: amlennon@jhmi.edu.

PMID: 26253305
PMCID: PMC4782782
DOI: 10.1053/j.gastro.2015.07.041

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.

Keywords: Diagnosis; IPMN; Molecular; Pancreatic Cyst.

PubMed Disclaimer

Conflict of interest statement

The terms of these arrangements are being managed by the university in accordance with its conflict of interest policies.

References

1. Laffan TA, Horton KM, Klein AP, et al. Prevalence of unsuspected pancreatic cysts on MDCT. AJR Am J Roentgenol. 2008;191:802–807. - PMC - PubMed
1. Lee KS, Sekhar A, Rofsky NM, et al. Prevalence of incidental pancreatic cysts in the adult population on MR imaging. Am J Gastroenterol. 2010;105:2079–2084. - PubMed
1. Lennon AM, Wolfgang C. Cystic neoplasms of the pancreas. J Gastrointest Surg. 2013;17:645–653. - PubMed
1. Bosman FT World Health Organization. WHO classification of tumours of the digestive system. Lyon: International Agency for Research on Cancer; 2010. International Agency for Research on Cancer.
1. Law JK, Ahmed A, Singh VK, et al. A systematic review of solid-pseudopapillary neoplasms: are these rare lesions? Pancreas. 2014;43:331–337. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Medical
- ClinicalTrials.gov
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A combination of molecular markers and clinical features improve the classification of pancreatic cysts

Affiliations

A combination of molecular markers and clinical features improve the classification of pancreatic cysts

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Research Materials

Miscellaneous