Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia

Mitsuro Kanda, Yoshihiko Sadakari, Michael Borges, Mark Topazian, James Farrell, Sapna Syngal, Jeffrey Lee, Ihab Kamel, Anne Marie Lennon, Spencer Knight, Sho Fujiwara, Ralph H. Hruban, Marcia Irene Canto, Michael Goggins

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

BACKGROUND and 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.

Original languageEnglish (US)
Pages (from-to)719-730.e5
JournalClinical Gastroenterology and Hepatology
Volume11
Issue number6
DOIs
StatePublished - Jun 2013

Keywords

  • Biomarker
  • Diagnostic
  • Early detection
  • Tumor

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    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. (2013). Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. Clinical Gastroenterology and Hepatology, 11(6), 719-730.e5. https://doi.org/10.1016/j.cgh.2012.11.016