Medline ® Abstract for Reference 103
of 'Familial risk factors for pancreatic cancer and screening of high-risk patients'
Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia.
Kanda M, Sadakari Y, Borges M, Topazian M, Farrell J, Syngal S, Lee J, Kamel I, Lennon AM, Knight S, Fujiwara S, Hruban RH, Canto MI, Goggins M
Clin Gastroenterol Hepatol. 2013 Jun;11(6):719-30.e5. Epub 2012 Nov 28.
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.
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.