フルカワ　トオル   Furukawa Tooru   古川　徹    所属   医学部 医学科（東京女子医科大学病院）    職種   客員教授
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	責任著者
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