Expression and prognostic significance of 14-3-3 sigma and ERM family protein expression in periampullary neoplasms

Abstract

Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5’ region of 14-3-3 sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3 sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 non-invasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003.

244 (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3 sigma and ERM protein expression. Expression of 14-3-3 sigma and ERM protein was more likely in poorly differentiated cancers (p=0.00005), and their expression was associated with poor survival in univariate analysis (p=0.09). By multivariate analysis, patients whose cancers expressed 14-3-3 sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p=0.14). Aberrant expression of 14-3-3 sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.