A Combination of Molecular Markers and Clinical Features Improve the Classification of Pancreatic Cysts
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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.
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In mucinous pancreatic cysts, cyst fluid has been demonstrated to be an attractive substrate for demonstrating aberrant somatic mutations, microRNAs or proteins, which are correlated with either the presence of mucinous epithelium per se or the progression to high-grade dysplasia and cancer.
“In the context of mucinous pancreatic cysts, cyst fluid has been demonstrated to be an attractive substrate for demonstrating aberrant somatic mutations, microRNAs or proteins, which are then correlated with either the presence of mucinous epithelium per se or the progression to high-grade dysplasia and cancer.60,61”
From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [61]
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Experimental — accuracy not yet measuredThe use of high-risk groups as controls and combining molecular markers with clinical features is an important consideration when identifying biomarkers capable of selecting populations at highest risk of pancreatic ductal adenocarcinoma for screening.
“Moreover, the use of high-risk groups as controls and combining molecular markers with clinical features is an important consideration when identifying biomarkers capable of selecting populations at highest risk of development of pancreatic ductal adenocarcinoma for screening.75”
From Early detection of pancreatic cancer (2020) · cites this paper as [75]
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Self-citationImproving outcomes of patients with pancreatic cancer
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WNT Ligand Dependencies in Pancreatic Cancer
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Self-citationAnalysis of Pancreatic Cyst Fluid
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Validation of Biomarkers for Early Detection of Pancreatic Cancer
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Self-citationA genetic roadmap of pancreatic cancer: still evolving
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Precursor Lesions of Pancreatic Cancer
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Self-citationCyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas
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Self-citationPancreatic Ductal Adenocarcinoma: Molecular Pathology and Predictive Biomarkers
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GNAS mutations in primary mucinous and non-mucinous lung adenocarcinomas
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Self-citationFamilial Pancreatic Cancer: Current Perspectives
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Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts
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Self-citationOverexpression of SOX11 and TFE3 in Solid-Pseudopapillary Neoplasms of the Pancreas
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Self-citationMolecular and clinicopathological features of appendiceal mucinous neoplasms
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- Authors
- 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., Cummings, O. W., Brand, R. E., Zeh, H. J., Singhi, A. D., Scarpa, A., Salvia, R., Malleo, G., Zamboni, G., Falconi, M., Jang, J.-Y., Kim, S.-W., Kwon, W., Hong, S.-M., Song, K.-B., Kim, S. C., Swan, N., Murphy, J., Geoghegan, J., Brugge, W., Fernandez-Del Castillo, C., Mino-Kenudson, M., Schulick, R., Edil, B. H., Adsay, V., Paulino, J., van Hooft, J., Yachida, S., Nara, S., Hiraoka, N., Yamao, K., Hijioka, S., van der Merwe, S., Goggins, M., Canto, M. I., Ahuja, N., Hirose, K., Makary, M., Weiss, M. J., Cameron, J., Pittman, M., Eshleman, J. R., Diaz, L. A., Papadopoulos, N., Kinzler, K. W., Karchin, R., Hruban, R. H., Vogelstein, B., & Lennon, A. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Indiana University Bloomington (US)
- University of Pittsburgh (US)
- University of Verona (IT)
- IRCCS Ospedale San Raffaele (IT)
- Seoul National University (KR)
- Asan Medical Center (KR)
- St. Vincent's University Hospital (IE)
- Massachusetts General Hospital (US)
- University of Colorado Boulder (US)
- Emory University (US)
- Hospital Curry Cabral (PT)
- National Cancer Centre Japan (JP)
- Aichi Cancer Center (JP)
- Corresponding author
- Lennon, Anne Marie
- ORCID
- Springer, Simeon
- Wang, Yuxuan
- Jiao, Yuchen
- Blackford, Amanda
- Wolfgang, Christopher L.
- Tomita, Tyler
- Niknafs, Noushin
- Douville, Christopher
- Ptak, Janine
- Dobbyn, Lisa
- 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
- Geoghegan, Justin
- Brugge, William
- Mino-Kenudson, Mari
- Schulick, Richard
- Edil, Barish H.
- Adsay, Volkan
- Paulino, Jorge
- Yachida, Shinichi
- Nara, Satoshi
- Hiraoka, Nobuyoshi
- Yamao, Kenji
- Goggins, Michael
- Canto, Marcia Irene
- Ahuja, Nita
- Hirose, Kenzo
- Makary, Martin
- Weiss, Matthew J.
- Pittman, Meredith
- Eshleman, James R.
- Diaz, Luis A.
- Papadopoulos, Nickolas
- Kinzler, Kenneth W.
- Karchin, Rachel
- Hruban, Ralph H.
- Vogelstein, Bert
- Lennon, Anne Marie
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 149
- Issue
- 6
- Pages
- 1501-1510
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC4782782
- OpenAlex
- W1945428417
- Cited by
- 477
- References
- 25
- Citations by year
- 2026: 31 · 2025: 33 · 2024: 31 · 2023: 35 · 2022: 35 · 2021: 49 · 2020: 47 · 2019: 55 · 2018: 55 · 2017: 64 · 2016: 40 · 2015: 2
- FWCI
- 23.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- PubMed Central (acceptedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- Lustgarten Foundation
- Virginia and D.K. Ludwig Fund for Cancer Research
- National Cancer Institute (P50CA-62924, R37CA043460, P50CA062924, P30CA008748, P30CA006973)
- National Institute of General Medical Sciences (T32GM007309, T32GM007057, T32GM007814)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- pancreatic cysts, pancreatic cystic neoplasms, molecular markers, cyst classification, intraductal papillary mucinous neoplasm, serous cystadenoma, solid pseudopapillary neoplasm, mucinous cystic neoplasm, cyst fluid analysis, loss of heterozygosity, aneuploidy, tumor suppressor, BRAF, CDKN2A, CTNNB1, TP53, VHL, RNF43, SMAD4, unnecessary surgery, clinical decision-making
- MeSH terms
- Adult, Algorithms, Female, Genetic Testing, Humans, Male, Middle Aged, Mutation, Pancreas, Pancreatic Cyst, Phenotype, Predictive Value of Tests, Prognosis, Retrospective Studies, Biomarkers, Tumor, Genetic Predisposition to Disease
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