Document Detail

Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas.
MedLine Citation:
PMID:  22167000     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
BACKGROUND: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy.
METHODS: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs.
RESULTS: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%).
CONCLUSIONS: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.
Hanno Matthaei; Alexis L Norris; Athanasios C Tsiatis; Kelly Olino; Seung-Mo Hong; Marco dal Molin; Michael G Goggins; Marcia Canto; Karen M Horton; Keith D Jackson; Paola Capelli; Giuseppe Zamboni; Laura Bortesi; Toru Furukawa; Shinichi Egawa; Masaharu Ishida; Shigeru Ottomo; Michiaki Unno; Fuyuhiko Motoi; Christopher L Wolfgang; Barish H Edil; John L Cameron; James R Eshleman; Richard D Schulick; Anirban Maitra; Ralph H Hruban
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of surgery     Volume:  255     ISSN:  1528-1140     ISO Abbreviation:  Ann. Surg.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-16     Completed Date:  2012-03-20     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  326-33     Citation Subset:  AIM; IM    
Department of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Germany.
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MeSH Terms
Adenocarcinoma, Mucinous / genetics,  pathology
Aged, 80 and over
Carcinoma, Pancreatic Ductal / genetics,  pathology
Carcinoma, Papillary / genetics,  pathology
Clone Cells
Laser Capture Microdissection
Loss of Heterozygosity*
Middle Aged
Neoplasms, Multiple Primary / genetics,  pathology
Neoplasms, Second Primary / genetics,  pathology
Pancreatic Neoplasms / genetics*,  pathology*
Proto-Oncogene Proteins / genetics*
Retrospective Studies
Sequence Analysis, DNA
ras Proteins / genetics*
Grant Support
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC Proteins

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