Document Detail

Molecular characteristics and biological behaviours of the oncocytic and pancreatobiliary subtypes of intraductal papillary mucinous neoplasms.
MedLine Citation:
PMID:  21547907     Owner:  NLM     Status:  MEDLINE    
Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. Of those, pancreatobiliary and oncocytic types are recently recognized and relatively uncommon, and usually exhibit high-grade dysplasia. The biological properties and molecular characteristics of these two types have not been well documented. The few molecular studies of the oncocytic type showed absence of KRAS mutations commonly seen in the other subtypes, raising the possibility that the oncocytic type is distinct from the other subtypes. Thus, we examined clinicopathological features and molecular alterations of the two subtypes. The study cohort consisted of 12 pancreatobiliary and 18 oncocytic IPMN cases. KRAS, BRAF, and PIK3CA mutations and TP53, SMAD4, and β-catenin expression were analysed, and the results of molecular and clinicopathological profiles were compared between the two subtypes. KRAS mutations were identified in the oncocytic type, but less frequently than the pancreatobiliary type (17% versus 58%, p = 0.048). BRAF mutation was found in a single oncocytic tumour, and no PIK3CA mutations were seen in any of the study cohort. TP53 overexpression was less frequent in the oncocytic type than in the pancreatobiliary type (11% versus 58%, p = 0.013). Invasive components were present in 50% of the oncocytic and 92% of the pancreatobiliary types, with lymph node metastasis more frequently seen in the latter, corresponding to better outcomes in the former (5-year survival rates: 93% versus 32%, p = 0.014). Our demonstration of KRAS and BRAF mutations in the oncocytic-type IPMN supports a role for the activation of the RAS-MAPK pathway in this tumour type. However, the less frequent TP53 overexpression associated with the significantly lower rates of invasion and nodal disease in the oncocytic type correlates with better outcomes compared to the pancreatobiliary type.
Hong D Xiao; Hiroshi Yamaguchi; Dora Dias-Santagata; Yuko Kuboki; Sara Akhavanfard; Takashi Hatori; Masakazu Yamamoto; Keiko Shiratori; Makio Kobayashi; Michio Shimizu; Carlos Fernandez-Del Castillo; Mari Mino-Kenudson; Toru Furukawa
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Publication Detail:
Type:  Journal Article     Date:  2011-05-05
Journal Detail:
Title:  The Journal of pathology     Volume:  224     ISSN:  1096-9896     ISO Abbreviation:  J. Pathol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-04     Completed Date:  2011-09-09     Revised Date:  2012-06-21    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  508-16     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
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MeSH Terms
Adenocarcinoma, Mucinous / genetics*,  metabolism,  pathology,  secondary
Aged, 80 and over
Carcinoma, Pancreatic Ductal / genetics*,  metabolism,  pathology,  secondary
Follow-Up Studies
Lymphatic Metastasis
Middle Aged
Neoplasm Invasiveness
Neoplasm Proteins / metabolism
Pancreatic Neoplasms / genetics*,  metabolism,  pathology
Point Mutation
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins B-raf / genetics
Survival Analysis
Young Adult
ras Proteins / genetics
Reg. No./Substance:
0/KRAS protein, human; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; EC protein, human; EC Proteins B-raf; EC Proteins

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