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Cited by 181Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsPancreatitis Pathology and Treatment

Mutant TP53 in Duodenal Samples of Pancreatic Juice From Patients With Pancreatic Cancer or High-Grade Dysplasia

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Kanda, Mitsuro, Sadakari, Yoshihiko, Borges, Michael, Topazian, Mark, Farrell, James, Syngal, Sapna, Lee, Jeffrey, Kamel, Ihab +6 more·2013·Clinical Gastroenterology and Hepatology
DOI 10.1016/j.cgh.2012.11.016PMC PMC3600161
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Abstract

Background & aims Imaging tests can identify patients with pancreatic neoplastic cysts but not microscopic dysplasia. We investigated whether mutant TP53 can be detected in duodenal samples of secretin-stimulated pancreatic juice, and whether this assay can be used to screen for high-grade dysplasia and invasive pancreatic cancer. Methods We determined the prevalence of mutant TP53 in microdissected pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and invasive adenocarcinomas. TP53 mutations were quantified by digital high-resolution melt-curve analysis and sequencing of secretin-stimulated pancreatic juice samples, collected from duodena of 180 subjects enrolled in Cancer of the Pancreas Screening trials; patients were enrolled because of familial and/or inherited predisposition to pancreatic cancer, or as controls. Results TP53 mutations were identified in 9.1% of intermediate-grade IPMNs (2 of 22), 17.8% of PanIN-2 (8 of 45), 38.1% of high-grade IPMNs (8 of 21), 47.6% of PanIN-3 (10 of 21), and 75% of invasive pancreatic adenocarcinomas (15 of 20); no TP53 mutations were found in PanIN-1 lesions or low-grade IPMNs. TP53 mutations were detected in duodenal samples of pancreatic juice from 29 of 43 patients with pancreatic ductal adenocarcinoma (67.4% sensitivity; 95% confidence interval, 0.52-0.80) and 4 of 8 patients with high-grade lesions (PanIN-3 and high-grade IPMN). No TP53 mutations were identified in samples from 58 controls or 55 screened individuals without evidence of advanced lesions. Conclusions We detected mutant TP53 in secretin-stimulated pancreatic juice samples collected from duodena of patients with high-grade dysplasia or invasive pancreatic cancer. Tests for mutant TP53 might be developed to improve the diagnosis of and screening for pancreatic cancer and high-grade dysplasia. Clinical Trial numbers: NCT00438906 and NCT00714701.

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  • TP53 mutations are prevalent in pancreatic lesions: 9.1% of intermediate-grade IPMNs, 17.8% of PanIN-2, 38.1% of high-grade IPMNs, 47.6% of PanIN-3 and 75% of invasive ductal adenocarcinomas.

    “TP53 mutations are prevalent in various pancreatic lesions, including 9.1% of intermediate-grade IPMNs, 17.8% of PanIN-2, 38.1% of high-grade IPMNs, 47.6% of PanIN-3 and 75% of invasive ductal adenocarcinomas.”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [27]

  • TP53 mutations were absent in pancreatic fluid samples from subjects with normal pancreas or chronic pancreatitis.

    “Notably, TP53 mutations were absent in pancreatic fluid samples from subjects with normal pancreas or chronic pancreatitis [27].”

    From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [27]

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References 34 · Cited by 181

Research works printed but not linked: 28

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Authors
Kanda, M., Sadakari, Y., Borges, M., Topazian, M., Farrell, J., Syngal, S., Lee, J., Kamel, I., Lennon, A. M., Knight, S., Fujiwara, S., Hruban, R. H., Canto, M. I., & Goggins, M.
Affiliations
  • Johns Hopkins University (US)
  • Mayo Clinic (US)
  • Dana-Farber Cancer Institute (US)
  • University of California, Los Angeles (US)
  • The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Goggins, Michael
ORCID
Venue
Clinical Gastroenterology and Hepatology
Publisher
Elsevier BV
Published
2013-06
Volume
11
Issue
6
Pages
719-730.e5
ISSN
1542-3565 (ISSN-L)
DOI
10.1016/j.cgh.2012.11.016
PMC
PMC3600161
OpenAlex
W2149894487
Cited by
181
References
34
Citations by year
2026: 6 · 2025: 8 · 2024: 10 · 2023: 11 · 2022: 13 · 2021: 12 · 2020: 8 · 2019: 16 · 2018: 20 · 2017: 22 · 2016: 20 · 2015: 11 · 2014: 17 · 2013: 7
FWCI
5.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Clinical Gastroenterology and Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (RC2CA148376, R01CA120432, K24CA113433, RC2CA148346, P50CA062924, CA 62924)
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
mutant TP53, pancreatic cancer screening, high-grade dysplasia, pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, pancreatic ductal adenocarcinoma
MeSH terms
Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Pancreatic Juice, Pancreatic Neoplasms, Precancerous Conditions, Tumor Suppressor Protein p53, Mutant Proteins

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