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Preoperative GNAS and KRAS Testing in the Diagnosis of Pancreatic Mucinous Cysts
Abstract
PURPOSE: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. EXPERIMENTAL DESIGN: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. RESULTS: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). CONCLUSIONS: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.
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“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 [60]
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Cites
International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas
Tanaka, M., Fernández-del Castillo, C., Adsay, V., Chari, S., Falconi, M., Jang, J.-Y., Kimura, W., Levy, P., Pitman, M. B., Schmidt, C. M., et al. (2012) · Pancreatology · doi:10.1016/j.pan.2012.04.004 · Cited by 2,354
Presence of Somatic Mutations in Most Early-Stage Pancreatic Intraepithelial Neoplasia
Kanda, M., Matthaei, H., Wu, J., Hong, S., Yu, J., Borges, M., Hruban, R. H., Maitra, A., Kinzler, K., Vogelstein, B., et al. (2012) · Gastroenterology · doi:10.1053/j.gastro.2011.12.042 · Cited by 741
Cystic precursors to invasive pancreatic cancer
Matthaei, H., Schulick, R. D., Hruban, R. H., & Maitra, A. (2011) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2011.2 · Cited by 193
Flagged first, then by citations
Research works printed but not linked: 23
- Laffan, 2008, Prevalence of unsuspected pancreatic cysts on MDCT, AJR Am J Roentgenol, 191, 802, 10.2214/AJR.07.3340 · DOI
- Hruban, 2007, Precursors to pancreatic cancer, Gastroenterol Clin North Am, 36, 831, 10.1016/j.gtc.2007.08.012 · DOI
- Khalid, 2007, ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts, Am J Gastroenterol, 102, 2339, 10.1111/j.1572-0241.2007.01516.x · DOI
- Tanaka, 2006, International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas, Pancreatology, 6, 17, 10.1159/000090023 · DOI
- Nikiforova, 2013, Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts, Mod Pathol, 26, 1478, 10.1038/modpathol.2013.91 · DOI
- Wu, 2011, Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways, Proc Natl Acad Sci U S A, 108, 21188, 10.1073/pnas.1118046108 · DOI
- Wu, 2011, Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development, Sci Transl Med, 3, 92ra66, 10.1126/scitranslmed.3002543 · DOI
- Furukawa, 2011, Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas, Sci Rep, 1, 161, 10.1038/srep00161 · DOI
- Hruban, 2007, Tumors of the pancreas, 10.55418/9781933477022 · DOI
- Klimstra, 2009, An algorithmic approach to the diagnosis of pancreatic neoplasms, Arch Pathol Lab Med, 133, 454, 10.5858/133.3.454 · DOI
- Huang, 2006, Fine-needle aspiration of pancreatic serous cystadenoma: cytologic features and diagnostic pitfalls, Cancer, 108, 239, 10.1002/cncr.21911 · DOI
- Pitman, 2007, Endoscopic ultrasound-guided fine needle aspiration cytology of the pancreas: a morphological and multimodal approach to the diagnosis of solid and cystic mass lesions, Cytopathology, 18, 331, 10.1111/j.1365-2303.2007.00457.x · DOI
- Pitman, 2010, Pancreatic cysts: preoperative diagnosis and clinical management, Cancer Cytopathol, 118, 1, 10.1002/cncy.20059 · DOI
- Zhai, 2006, Pancreatic mucinous lesions: a retrospective analysis with cytohistological correlation, Diagn Cytopathol, 34, 724, 10.1002/dc.20561 · DOI
- Khalid, 2004, Use of microsatellite marker loss of heterozygosity in accurate diagnosis of pancreaticobiliary malignancy from brush cytology samples, Gut, 53, 1860, 10.1136/gut.2004.039784 · DOI
- Khalid, 2006, Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses, Am J Gastroenterol, 101, 2493, 10.1111/j.1572-0241.2006.00740.x · DOI
- Nodit, 2006, Endoscopic ultrasound-guided fine needle aspirate microsatellite loss analysis and pancreatic endocrine tumor outcome, Clin Gastroenterol Hepatol, 4, 1474, 10.1016/j.cgh.2006.07.017 · DOI
- Dal Molin, 2013, Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas, Ann Surg Oncol, 20, 3802, 10.1245/s10434-013-3096-1 · DOI
- Siddiqui, 2013, EUS-guided pancreatic fluid aspiration for DNA analysis of KRAS and GNAS mutations for the evaluation of pancreatic cystic neoplasia: a pilot study, Gastrointest Endosc, 77, 669, 10.1016/j.gie.2012.11.009 · DOI
- Panarelli, 2012, Commercial molecular panels are of limited utility in the classification of pancreatic cystic lesions, Am J Surg Pathol, 36, 1434, 10.1097/PAS.0b013e31825d534a · DOI
- Lohr, 2001, p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis, Gastrointest Endosc, 53, 734, 10.1067/mge.2001.112711 · DOI
- Yamaguchi, 1999, Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation, Clin Cancer Res, 5, 1147
- Yan, 2005, Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk groups, Gastroenterology, 128, 2124, 10.1053/j.gastro.2005.03.006 · DOI
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Sorted by citations
European evidence-based guidelines on pancreatic cystic neoplasms
The European Study Group on Cystic Tumours of the Pancreas (2018) · Gut · doi:10.1136/gutjnl-2018-316027 · Cited by 1,417
Early Detection of Pancreatic Cancer: Opportunities and Challenges
Singhi, A. D., Koay, E. J., Chari, S. T., & Maitra, A. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.01.259 · Cited by 841
Self-citationSinghi, A. D., McGrath, K., Brand, R. E., Khalid, A., Zeh, H. J., Chennat, J. S., Fasanella, K. E., Papachristou, G. I., Slivka, A., Bartlett, D. L., et al. (2018) · Gut · doi:10.1136/gutjnl-2016-313586 · Cited by 405
Self-citationArtificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review
Kenner, B., Chari, S. T., Kelsen, D., Klimstra, D. S., Pandol, S. J., Rosenthal, M., Rustgi, A. K., Taylor, J. A., Yala, A., Abul-Husn, N., et al. (2021) · Pancreas · doi:10.1097/mpa.0000000000001762 · Cited by 158
RAS mutations in human cancers: Roles in precision medicine
Murugan, A. K., Grieco, M., & Tsuchida, N. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.06.007 · Cited by 146
Metadata
- Authors
- Singhi, A. D., Nikiforova, M. N., Fasanella, K. E., McGrath, K. M., Pai, R. K., Ohori, N. P., Bartholow, T. L., Brand, R. E., Chennat, J. S., Lu, X., Papachristou, G. I., Slivka, A., Zeh, H. J., Zureikat, A. H., Lee, K. K., Tsung, A., Mantha, G. S., & Khalid, A.
- Affiliations
- Departments of 1Pathology,
- 2Medicine, and
- VA Pittsburgh Healthcare System (US)
- University of Pittsburgh Medical Center (US)
- Corresponding author
- Singhi, Aatur D.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2014-08-13
- Volume
- 20
- Issue
- 16
- Pages
- 4381-4389
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2139069376
- Cited by
- 207
- References
- 3
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 18 · 2023: 14 · 2022: 11 · 2021: 19 · 2020: 16 · 2019: 27 · 2018: 20 · 2017: 27 · 2016: 16 · 2015: 13
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Pancreas Foundation
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, GNAS mutation, KRAS mutation, pancreatic cyst fluid, endoscopic ultrasound-guided fine-needle aspiration, preoperative genetic testing, sensitivity and specificity, pancreatic neuroendocrine tumors, serous cystadenoma, pancreatic ductal adenocarcinoma, pancreatic cysts
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Adenocarcinoma, Mucinous, Carcinoma, Papillary, Chromogranins, Female, Follow-Up Studies, Humans, Male, Middle Aged, Mutation, Neoplasm Staging, Pancreatic Cyst, Pancreatic Neoplasms, Preoperative Care, Prognosis, Proto-Oncogene Proteins, Biomarkers, Tumor, Proto-Oncogene Proteins p21(ras), Cystadenoma, Serous, ras Proteins, GTP-Binding Protein alpha Subunits, Gs, Cyst Fluid, Carcinoma, Pancreatic Ductal, Biopsy, Fine-Needle, Young Adult
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