Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas

Yuko Kuboki, Kyoko Shimizu, Takashi Hatori, Masakazu Yamamoto, Noriyuki Shibata, Keiko Shiratori, Toru Furukawa

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Objectives: We aimed to identify molecular biomarkers for assessing the progression of intraductal papillarymucinous neoplasmof the pancreas (IPMN).Methods:We retrospectively investigatedmolecular aberrations and their associations with clinicopathological features in 172 IPMNs.Results: GNAS and KRAS mutations were detected in 48% and 56% of IPMNs, respectively. No mutations of EGFR, PIK3CA GNAO1, GNAQ, or GNAI2 were observed. Significant associations were observed between IPMN morphological types and GNAS mutations, KRAS mutations, the expression of phosphorylated MAPK (pMAPK), AKT, and phosphorylated AKT (pAKT), nuclear accumulation of β-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear β-catenin, and SMAD4 loss; and prognosis and SMAD4 loss and TP53 overexpression. Multivariate analysis to compare prognostic impacts of multiple molecular features revealed that TP53 overexpression was an independent prognostic factor (P = 0.030; hazard ratio, 5.533).Conclusions: These results indicate that mutations in GNAS and KRAS, the expression of EGFR and pMAPK, the nuclear β-catenin, SMAD4 loss, and TP53 overexpression may be relevant for assessing the clinical course of IPMN, including its progression into different morphological types, invasion, and prognosis.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalPancreas
Volume44
Issue number2
DOIs
Publication statusPublished - 2015 Jan 1
Externally publishedYes

Keywords

  • GNAS
  • KRAS
  • Pancreatic cancer
  • SMAD4
  • TP53
  • β-catenin

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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