Role of epithelial-to-mesenchymal transition in pancreatic ductal carcinoma with and without intraepithelial neoplasia

Pancreatic intraepithelial neoplasia (PanIN) is one of the important precancerous lesions of pancreatic ductal adenocarcinoma (PDAC), which is identified microscopically in resected samples. PanIN is reported as one of the prognostic factors for PDAC, but the detailed pathways are unclear and controversial. PanINs with high expression levels of epithelial-to-mesenchymal transition transcription factors (EMT-TFs) have been linked to favorable prognosis for the accompanying PDACs. However, the relationship between PanIN and EMT-TF expression in PDAC tumors is still unknown. In this study, we investigated 69 resected specimens of PDAC. PanIN was identified in 34 (49.3%) specimens; among these, 28 specimens harbored high-grade PanIN (HG-PanIN). SLUG and ZEB1 exhibited higher expression in PDACs with HG-PanIN than in PDACs without HG-PanIN (P=0.041 for SLUG and P=0.024 for ZEB1). Survival analysis showed no significant difference in overall survival rates with or without HG-PanIN (P=0.54). Multivariate analysis suggested that HG-PanIN was not a prognostic factor (hazard ratio 0.71, 95% confidence interval, 0.36-1.38, P=0.30). Our results suggest an existence of novel subgroup of PDAC characterized by the presence of PanIN and the expression of different EMT-TFs, which could be therapeutic targets for precision medicine in PDAC.