PMID- 25423558
OWN - NLM
STAT- MEDLINE
DCOM- 20151123
LR  - 20220316
IS  - 1536-4828 (Electronic)
IS  - 0885-3177 (Linking)
VI  - 44
IP  - 2
DP  - 2015 Mar
TI  - Molecular biomarkers for progression of intraductal papillary mucinous neoplasm 
      of the pancreas.
PG  - 227-35
LID - 10.1097/MPA.0000000000000253 [doi]
AB  - 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.
FAU - Kuboki, Yuko
AU  - Kuboki Y
AD  - From the *Institute for Integrated Medical Sciences, daggerDepartment of 
      Gastroenterology, double daggerDepartment of Gastroenterological Surgery, Institute of 
      Gastroenterology,  section signDepartment of Pathology, and  parallelDepartment of Surgical 
      Pathology, Tokyo Women's Medical University, Tokyo, Japan.
FAU - Shimizu, Kyoko
AU  - Shimizu K
FAU - Hatori, Takashi
AU  - Hatori T
FAU - Yamamoto, Masakazu
AU  - Yamamoto M
FAU - Shibata, Noriyuki
AU  - Shibata N
FAU - Shiratori, Keiko
AU  - Shiratori K
FAU - Furukawa, Toru
AU  - Furukawa T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pancreas
JT  - Pancreas
JID - 8608542
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Chromogranins)
RN  - 0 (KRAS protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (SMAD4 protein, human)
RN  - 0 (Smad4 Protein)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GNAS protein, human)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gs)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Biomarkers, Tumor/*analysis/*genetics
MH  - Chi-Square Distribution
MH  - Chromogranins
MH  - DNA Mutational Analysis
MH  - Disease Progression
MH  - ErbB Receptors/analysis/genetics
MH  - GTP-Binding Protein alpha Subunits, Gs/genetics
MH  - Humans
MH  - Immunohistochemistry
MH  - Kaplan-Meier Estimate
MH  - Mitogen-Activated Protein Kinases/analysis
MH  - Multivariate Analysis
MH  - Mutation
MH  - Neoplasm Recurrence, Local
MH  - Neoplasms, Cystic, Mucinous, and 
      Serous/*chemistry/*genetics/mortality/pathology/therapy
MH  - Pancreatic Neoplasms/*chemistry/*genetics/mortality/pathology/therapy
MH  - Phosphorylation
MH  - Predictive Value of Tests
MH  - Proportional Hazards Models
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Smad4 Protein/analysis
MH  - Time Factors
MH  - Treatment Outcome
MH  - Tumor Suppressor Protein p53/analysis
MH  - ras Proteins/genetics
EDAT- 2014/11/26 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/11/26 06:00
PHST- 2014/11/26 06:00 [entrez]
PHST- 2014/11/26 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1097/MPA.0000000000000253 [doi]
PST - ppublish
SO  - Pancreas. 2015 Mar;44(2):227-35. doi: 10.1097/MPA.0000000000000253.