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

96 Citations (Scopus)

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
JournalClinical Gastroenterology and Hepatology
Volume11
Issue number6
DOIs
Publication statusPublished - Jan 1 2013
Externally publishedYes

Fingerprint

Pancreatic Juice
Pancreatic Neoplasms
Secretin
Mutation
Neoplasms
Adenocarcinoma
Pancreatic Cyst
Early Detection of Cancer
Clinical Trials
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. / Kanda, Mitsuro; Sadakari, Yoshihiko; Borges, Michael; Topazian, Mark; Farrell, James; Syngal, Sapna; Lee, Jeffrey; Kamel, Ihab; Lennon, Anne Marie; Knight, Spencer; Fujiwara, Sho; Hruban, Ralph H.; Canto, Marcia Irene; Goggins, Michael.

In: Clinical Gastroenterology and Hepatology, Vol. 11, No. 6, 01.01.2013.

Research output: Contribution to journalArticle

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 2013, 'Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia', Clinical Gastroenterology and Hepatology, vol. 11, no. 6. https://doi.org/10.1016/j.cgh.2012.11.016
Kanda, Mitsuro ; Sadakari, Yoshihiko ; Borges, Michael ; Topazian, Mark ; Farrell, James ; Syngal, Sapna ; Lee, Jeffrey ; Kamel, Ihab ; Lennon, Anne Marie ; Knight, Spencer ; Fujiwara, Sho ; Hruban, Ralph H. ; Canto, Marcia Irene ; Goggins, Michael. / Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia. In: Clinical Gastroenterology and Hepatology. 2013 ; Vol. 11, No. 6.
@article{88e79cb747544a0da9e47addbd5e3ee0,
title = "Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia",
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.",
author = "Mitsuro Kanda and Yoshihiko Sadakari and Michael Borges and Mark Topazian and James Farrell and Sapna Syngal and Jeffrey Lee and Ihab Kamel and Lennon, {Anne Marie} and Spencer Knight and Sho Fujiwara and Hruban, {Ralph H.} and Canto, {Marcia Irene} and Michael Goggins",
year = "2013",
month = "1",
day = "1",
doi = "10.1016/j.cgh.2012.11.016",
language = "English",
volume = "11",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "6",

}

TY - JOUR

T1 - Mutant TP53 in duodenal samples of pancreatic juice from patients with pancreatic cancer or high-grade dysplasia

AU - Kanda, Mitsuro

AU - Sadakari, Yoshihiko

AU - Borges, Michael

AU - Topazian, Mark

AU - Farrell, James

AU - Syngal, Sapna

AU - Lee, Jeffrey

AU - Kamel, Ihab

AU - Lennon, Anne Marie

AU - Knight, Spencer

AU - Fujiwara, Sho

AU - Hruban, Ralph H.

AU - Canto, Marcia Irene

AU - Goggins, Michael

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878150670&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878150670&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2012.11.016

DO - 10.1016/j.cgh.2012.11.016

M3 - Article

C2 - 23200980

AN - SCOPUS:84878150670

VL - 11

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 6

ER -