Abstract： Objective:To investigate the expression of human epidermal growth factor receptor 2 (HER2) in pancreatic ductal adenocarcinoma(PDAC) and its relationship with the prognosis of patients with PDAC.Methods:From January 2001 to December 2012, 109 paraffin embedded PDAC tissue samples and 27 normal pancreatic tissue samples were collected from the Department of Pathology, Huadong Hospital Affiliated to Fudan University. The expression of HER2 protein in pancreatic tissue was detected by immunohistochemical Envision two-step method. HER2 expression was evaluated according to Hercept test, and its relationship with clinicopathological features and survival time was analyzed.Results:The expression of HER2 protein was negative (-) in 29.4% of PDAC tissues, weakly positive (+ ) in 35.8%, positive (+ + ) in 25.7% and strongly positive (+ + + ) in 9.2%, respectively, and the overexpression rate (+ + , + + + ) was 34.9%; the negative (-) and weakly positive (+ ) expression of HER2 protein in normal pancreatic tissues accounted for 88.9% and 11.1% respectively. There was no expression with positive (+ + ) or strongly positive (+ + + ), therefore, the overexpression rate was 0. The overexpression rate of HER2 protein in PDAC and normal pancreatic tissues was significantly different ( P=0.000). The expression of HER2 protein was significantly correlated with age, and the expression of HER2 protein in patients with PDAC over 65 years old was significantly higher than that in patients with PDAC under 65 years old ( P=0.043), but not with gender, tumor location, tumor grade, T stage, N stage and nerve invasion (all P>0.05). Univariate Cox proportional hazards analysis showed that HER2 expression was associated with postoperative survival time of patients with PDAC ( P=0.032). Multivariate Cox proportional hazards analysis showed that HER2 expression was an independent prognostic factor for survival of patients with PDAC ( P=0.040). The median survival period of patients with HER2 expression + + + was significantly longer than that of patients with HER2 expression -~+ + (128.4 months vs 21.5 months), and the difference was statistically significant ( P=0.038). Conclusions:The overexpression of HER2 in PDAC tissue was related to the age of patients. The survival time of patients with HER2 strongly positive PDAC was significantly longer. HER2 can be considered as an index to evaluate the biological behavior and prognosis of PDAC.