Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN)

Abstract

Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis. We analysed the expression of p21, p27, p53 and Ki-67, in 210 ductal pancreatic adenocarcinomas, 40 PanIN-3 cases and 40 normal controls combined in a tissue microarray. The results were correlated with clinicopathological and follow-up data. Our study revealed a differential p27, p21, p53, and Ki-67 expression between ductal adenocarcinoma, PanIN-3 and normal pancreas. p27 expression progressively decreased from normal pancreas to PanIN and to pancreatic cancer. Decreased p27 and increased p53 expression showed a significant association with the T stage. A Ki-67 >5% correlated with reduced survival. In pancreatic cancer, loss of p27 and increased p53 expression is associated with a more aggressive phenotype. p27 may play an important role in pancreatic carcinogenesis. A Ki-67 >5% independently predicted poor outcome.