Background: Pancreatic duct adenocarcinoma (PDAC) is an aggressive neoplasm. It shows progressive and cumulative genetic mutations, with subsequent development of therapy-resistant clones. Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein that is normally involved in cellular proliferation and differentiation. Overexpression of HER2 was detected in several human malignant neoplasms. HER2 was successfully targeted in breast carcinoma and gastric carcinoma with improved prognosis in these neoplasms.
Aim: This study aimed to evaluate the immune expression of HER2 in PDAC, and to correlate HER2 expression with a variety of clinical and pathological parameters.  
Methods: Formalin-fixed, paraffin-embedded tissue blocks from 37 patients with PDAC were studied. Two tissue sections were prepared from each tumor-laden tissue block; one section was stained by hematoxylin and eosin to confirm the diagnosis of PDAC, determine tumor grade, and detect perineural and/or vascular invasion. The other section was stained immunohistochemically by an anti-human HER2 antibody.
Results: Lympho-vascular invasion was detected in 89.2% of cases, it was associated with both advanced pathological tumor stages (p = 0.023) and regional lymph node involvement (p = 0.028). Circumferential perineural invasion was found in 75.7% of cases and correlated significantly with the advanced tumor stage (p < 0.0001), high tumor grade (p = 0.014), and regional lymph node involvement (p = 0.002). Positive expression of HER2 was detected in 51.4% of cases, HER2 positivity was significantly associated with grade III tumors (p = 0.046), advanced pathological stages (p  = 0.002), regional lymph node involvement (p = 0.005), perineural invasion (p < 0.0001) and lymphovascular invasion (p = 0.046).
Conclusion: HER2 protein is over-expressed in advanced stages of PDAC and is associated with poor prognosis pathologic features. Targeting HER2 in therapeutic protocols may improve the future prognosis of PDAC.