Mutational Patterns in Pancreatic Juice of Intraductal Papillary Mucinous Neoplasms and Concomitant Pancreatic Cancer

Pancreas. 2019 Sep;48(8):1032-1040. doi: 10.1097/MPA.0000000000001371.

Abstract

Objectives: The aims of this study were to identify genetic characteristics of intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic ductal carcinoma (PDC) and to detect these markers using pancreatic juice.

Methods: From 76 cases, 102 tissues were obtained: 29 cases were noninvasive IPMN, 18 were PDC derived from IPMN (D-PDC; noninvasive part, n = 16; invasive part, n = 18), and 29 were PDC concomitant with IPMN (C-PDC; IPMN part, n = 10; PDC part, n = 29). Moreover, pancreatic juice samples from 28 cases were obtained (noninvasive IPMN, n = 13; D-PDC, n = 7; C-PDC, n = 8). Fifty-one cancer-related genes were analyzed by next-generation sequencing.

Results: TP53 mutation rates in D-PDC, C-PDC, and noninvasive IPMN were 67%, 66%, and 10%, respectively. Moreover, KRAS mutational patterns between 2 simultaneous tumors differed in 1 (6.3%) of the 16 D-PDC cases and in 8 (80%) of the 10 C-PDC cases (P = 0.0006). TP53 or multiple KRAS mutations were detected using pancreatic juice more frequently in C-PDC cases than in noninvasive IPMN cases (75% and 23%, respectively, P = 0.03).

Conclusions: Multiple KRAS mutations along with TP53 mutation are genetic markers for C-PDC, which could be detected using pancreatic juice preoperatively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Mucinous / diagnosis
  • Adenocarcinoma, Mucinous / genetics*
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / genetics*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Middle Aged
  • Mutation*
  • Pancreatic Juice / metabolism*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)