Expression of chosen cell cycle and proliferation markers in pancreatic intraepithelial neoplasia

Introduction
Pancreatic ductal adenocarcinoma is one of the most aggressive tumours that develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN). Deregulation of the cell cycle, responsible for uncontrolled cell proliferation, is an important phenomenon in the development of this cancer.

Aim
To evaluate the cell cycle and the expression of proliferation markers, namely Ki67, PCNA, and cyclin D1 in pancreatic intraepithelial neoplasia at its different stages of progression.

Material and methods
The study group consisted of 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), who also had pancreatic intraepithelial neoplasia. Expression of Ki67, PCNA, and Cyclin D1 was analysed immunohistochemically using appropriate antibodies.

Results
Statistically significant differences were demonstrated in Ki67, PCNA, and Cyclin D1 expression between normal pancreatic ducts and various stages of PanIN (p < 0.001). Expression of these proteins increased from normal pancreas to PanIN 1, 2, and 3. Expression of these proteins was higher in stages PanIN 1, 2, and 3 compared to normal pancreas. The expression of Ki67, PCNA, and cyclin D1 was associated with age (p < 0.001), Ki67 and PCNA with sex (p < 0.001), and PCNA with the type of primary disease (p = 0.031). Simultaneously, a directly proportional relationship was established between the expression of all proteins examined (p < 0.001).

Conclusions
An increase in the expression of Ki67, PCNA, and cyclin D1 suggests that these proteins may enhance epithelial cell proliferation and may influence the development of pancreatic intraepithelial neoplasia. Moreover, immunohistochemical assessment of Ki67, PCNA, and cyclin D1 expression may be helpful in the differential diagnosis of PanIN.