title: Loss of expression of the SWI/SNF chromatin remodeling subunit BRG1/SMARCA4 is frequently observed in intraductal papillary mucinous neoplasms of the pancreas.
abstract: A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P = .03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University, Baltimore, MD 21231, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Dal Molin
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.forename: Sachidanand
authors.initials: S
authors.lastname: Hebbar
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Francesca
authors.initials: F
authors.lastname: Scrimieri
authors.forename: Roeland F
authors.initials: RF
authors.lastname: de Wilde
authors.forename: Skye C
authors.initials: SC
authors.lastname: Mayo
authors.forename: Michael
authors.initials: M
authors.lastname: Goggins
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
authors.forename: Ming-Tseh
authors.initials: MT
authors.lastname: Lin
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Hanno
authors.initials: H
authors.lastname: Matthaei
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases