Abstract
BackgroundDeregulation of cell cycle takes place during the development of many cancers as well as pancreatic ductal adenocarcinoma (PDA), which develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN).AimsThe aim of this study was to evaluate and compare the expression of p16, p21, and p53 proteins taking part in the regulation of the cell cycle in normal pancreatic ducts and pancreatic intraepithelial neoplasia at its various advancing stages.MethodsThe expressions of p16, p21, and p53 were assessed immunohistochemically in 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), showing also pancreatic intraepithelial neoplasia. The results correlated with chosen clinicopathological parameters.ResultsOur study revealed a difference in p16, p21, and p53 expressions between normal pancreatic ducts and various stages of PanIN. p16 expression progressively decreased, whereas p21 and p53 increased from normal pancreas to PanIN 1, 2, and 3. The expression of p21 was associated with age, p53 with PanIN location in the pancreas and p16 with the type of primary diseases. Simultaneously, we observed a directly proportional relationship between the expression of p21 and p53 proteins and inversely proportional between the p16 and the p21 and p53 proteins.Conclusionsp16, p21, and p53 proteins play an important role in the deregulation of the cell cycle and participate in the development of pancreatic intraepithelial neoplasia. Immunohistochemical evaluation of their expressions may be helpful in the diagnosis of PanIN.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common epithelial cancers of the exocrine pancreas representing more than 95% of malignant tumors of this organ [1]
Deregulation of the cell cycle occurs during the development of pancreatic ductal adenocarcinoma, in which, as it was demonstrated, there is a series of mutation tumor supressor genes—p16, TP53, DPC4, BRCA2—and oncogenes such as KRAS and c-erbB-2 [9]
These mutations have been observed in pancreatic intraepithelial neoplasia, which is a precursor lesion of pancreatic ductal adenocarcinoma
Summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most common epithelial cancers of the exocrine pancreas representing more than 95% of malignant tumors of this organ [1]. It is classified on the 12th position in terms of cancer incidence in the world but is the fourth leading cause of cancer deaths. Detection and treatment of precursor lesions would prevent the further progression and development of invasive cancer as observed in the case of colorectal, breast, and cervical cancer, where the screening test significantly reduced the percentage of morbidity and mortality due to cancer [3]. Aims The aim of this study was to evaluate and compare the expression of p16, p21, and p53 proteins taking part in the regulation of the cell cycle in normal pancreatic ducts and pancreatic intraepithelial neoplasia at its various advancing stages
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