Furukawa, Toru
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Visiting Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas.
Journal Formal name:Pancreas
Abbreviation:Pancreas
ISSN code:15364828/08853177
Publisher Wolters Kluwer Health, Inc.
Volume, Issue, Page 44(2),pp.227-235
Author and coauthor KUBOKI Yuko†, SHIMIZU Kyoko, HATORI Takashi, YAMAMOTO Masakazu, SHIBATA Noriyuki, SHIRATORI Keiko, FURUKAWA Toru*
Authorship Corresponding author
Publication date 2015/03
Summary OBJECTIVES: We aimed to identify molecular biomarkers for assessing the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN). METHODS: We retrospectively investigated molecular 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 beta-catenin, SMAD4 loss, and TP53 overexpression; histological grades and the expression of EGFR, pMAPK, AKT, and pAKT, the nuclear beta-catenin, SMAD4 loss, and TP53 overexpression; invasive phenotypes and KRAS mutations, the nuclear beta-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 beta-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.
DOI 10.1097/MPA.0000000000000253
PMID 25423558