Aberrant gene expression in pancreatic ductal
adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (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 14-3-3sigma and the ERM
proteins (
Ezrin,
radixin,
Moesin) in a series of invasive periampullary
adenocarcinomas including 300 infiltrating pancreatic
adenocarcinomas, 54 ampullary
adenocarcinomas, and 33 noninvasive intraductal papillary
mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (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 14-3-3sigma and ERM
protein expression. Expression of 14-3-3sigma 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 14-3-3sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3sigma may contribute to the outcome of patients with pancreatic ductal
adenocarcinoma.