Loss of Expression of the SWI/SNF Chromatin Remodeling Subunit BRG1/SMARCA4 Is Frequently Observed in Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas

Marco Dal Molin, Seung-Mo Hong, Sachidanand Hebbar, Rajni Sharma, Francesca Scrimieri, Roeland de Wilde, Skye C. Mayo, Michael Goggins, Christopher L. Wolfgang, Richard D. Schulick, Ming-Tseh Lin, James R. Eshleman, Ralph H. Hruban, Anirban Maitra, Hanno Matthaei

Research output: Contribution to journalMeeting AbstractAcademicpeer-review

Abstract

Background: A better molecular characterization of Intraductal Papillary Mucinous Neoplasm (IPMN), the most frequent cystic precursor 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.

Methods: We evaluated Brg1 expression in IPMN in order to better understand its role in pancreatic carcinogenesis. Tissue microarrays (TMAs) of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were correlated with clinicopathologic parameters.

Results: Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable 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 (4 of 14 showed loss; 28%) (p=0.03). A complete loss of expression was observed in 5 of the 60 (8.3%) lesions. Finally, a decrease in Brg1 protein expression was found in a low-passage non-invasive IPMN cell line by Western blot analysis.

Conclusion: We provide first evidence that Brg1 expression is lost in IPMN.
Original languageEnglish
Pages (from-to)1318-1319
Number of pages2
JournalPancreas
Volume40
Issue number8
Publication statusPublished - Nov 2011
Externally publishedYes

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