Loss of BRG1/SMARCA4 Expression in Pancreatic Ductal Adenocarcinoma
M Lin, F Scrimieri, T Nguyen, CL Wolfgang, C Iacobuzio-Donahue, A Maitra, M Goggins, J Eshleman, K Olino, SE Kern, RH Hruban. Johns Hopkins University School of Medicine, Baltimore, MD
Background: Pancreatic ductal adenocarcinoma is an almost universally fatal disease, with a 5 year survival rate of approximately 5%. The coding genome of 24 human pancreatic cancers was recently sequenced (S. Jones et al., Science 2008) and the BRG1 (also known as SMARCA4) gene was found to be bi-allelically inactivated in one of the 24 cancers suggesting that BRG1 may function as a tumor suppressor gene in pancreatic cancer. An additional cancer with monoalleic inactivation was identified in the validation phase of the sequencing study. The prevalence of BRG1 gene inactivation in a larger series of pancreatic cancers has not been defined.
Design: Formalin-fixed, paraffin-embedded tissues from the 2 patients with mutations of the gene were immunohistochemical labeled with a monoclonal antibody to BRG1 (amino acids 209-296; Santa Cruz Biotechnology, Santa Cruz, CA) using standard methods. Subsequently, tissue micro-arrays from 397 patients with invasive pancreatic ductal adenocarcinoma and 44 patients with pancreatic intraepithelial neoplasia were immunolabeled using the anti-BRG1 antibody. Each tissue micro-arrays included two cores of normal tissue and two of tumor.
Results: As expected, the primary and metastases from the patient with biallelic inactivation had a complete loss of BRG1 protein expression, while BRG1 expression was retained in the neoplastic cells of the patient with monoalleic inactivation. Loss of BRG1 expression was identified in only two (0.5%) of the 397 cases with invasive pancreatic ductal adenocarcinoma and none of the 44 cases of pancreatic intraepithelial neoplasia.
Conclusions: These data indicate that loss of BRG1 protein expression is uncommon in pancreatic ductal adenocarcinoma, and suggest that BRG1 gene inactivation is a relatively rare event in pancreatic cancer. Further studies are needed to elucidate the possible pathogenesis of BRG1 mutations in rare pancreatic ductal adenocarcinomas.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 210, Tuesday Afternoon