シミズ　キヨウコ   SHIMIZU Kyoko   清水　京子    所属   その他 その他    職種   非常勤嘱託
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas.
掲載誌名	正式名：Pancreas 略　 称：Pancreas ISSNコード：15364828/08853177
出版社	Wolters Kluwer Health, Inc.
巻・号・頁	44(2),pp.227-235
著者・共著者	KUBOKI Yuko†, SHIMIZU Kyoko, HATORI Takashi, YAMAMOTO Masakazu, SHIBATA Noriyuki, SHIRATORI Keiko, FURUKAWA Toru*
担当区分	2nd著者
発行年月	2015/03
概要	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