Actin-Bundling Proteins (Actinin-4 and Fascin-1) are Involved in the Development of Pancreatic Intraepithelial Neoplasia (PanIN)

Abstract

Fascin-1 and actinin-4 are involved in key processes of tumor cell adhesion, migration and metastasis. Actinin-4 plays an important role in promotion of cell proliferation, whereas fascin-1 regulates cellular motility. Its over-expression leads to the loss of cell adhesion and metastasis. The aim of our study was to assess fascin-1 and actinin-4 expression in normal pancreatic ducts and in pancreatic intraepithelial neoplasia (PanIN) - precursor lesion of pancreatic ductal adenocarcinoma (PDAC). The study involved 70 patients treated surgically due to PDAC, cysts and pancreatitis, who had also been diagnosed with pancreatic intraepithelial neoplasia. Fascin-1 and actinin-4 expressions were evaluated using the immunohistochemistry method. A statistically significant relationship was observed between the expression of fascin-1 and actinin-4 (cytoplasmic) and patients' age (P=0.01, P=0.002, respectively). The expression of fascin-1 and actinin-4 was associated with the diagnosis (P<0.001,P=0.04, respectively). Statistical analysis revealed correlations of fascin-1 and actinin-4 expressions with the presence and grade of PanIN (P < 0.001, P=0.002, respectively). The expression of these proteins was observed in each degree of PanIN and increased with the pancreatic intraepithelial neoplasia progression. The expression of fascin-1 and actinin-4 is connected with the degree of PanIN advancement and depends on the type of the primary disease. Overexpression of these proteins may be linked to cytological and architectural abnormalities observed in advanced PanIN. Elevated expression of fascin-1 and actinin-4 indicates the role of these proteins in the progression from PanIN to PDAC.