Pattern of expression of Delta-like ligand 4 (DLL-4) in patients with pancreatic ductal and ampullary adenocarcinomas and its clinicopathological prognostic implications

Abstract

Background: There is an increasing interest for Notch signalling pathway and particularly Delta-like ligand 4 (DLL4), a Notch ligand as potential therapeutic target to improve outcome for patients with pancreatic ductal adenocarcinoma (PDAC). Aim: characterize the expression of DLL4 in PDAC and ampullary adenocarcinoma (AA), evaluate their correlation with clinicopathologic features and patients' survival. Materials and Methods: In a retrospective study, using immunohistochemistry, we assessed the expression of DLL4 in 62 cases composed of 39 cases of PDAC and 23 cases of AA undergone Whipple and received adjuvant chemotherapy and radiotherapy. We assessed the expression level of DLL4 both in tumor cells and stromal vascular endothelial cells. The relationships of DLL4 expression with clinico-pathologic parameters and clinical outcome were evaluated.Results: There was no statistically significant relation between clinico-pathological parameters and DLL4 score expression in tumor cells of PDAC cases. However, there was statistically significant relation between DLL4 score expression in tumor cells of AA cases and tumor stage (p= 0.041). Also, there was no statistical significance regarding DLL4 expression in stromal cells in PDAC and AA cases and clinico-pathological parameters. Regarding survival functions for pancreatic & ampullary tumor cases; the median overall survival (OS) was 10 and 22 months for pancreatic (95% CI: 1-45) and ampullary tumors (95% CI: 1-69) respectively. OS for pancreatic and ampullary tumors was higher in cases with low DLL4 expression versus cases with high expressions with no statistically significance (P=0.48 & 0.09 respectively). The median Progression free survival (PFS) was 7 and 17.5 months for pancreatic (95% CI: 0-43) and ampullary tumors (95% CI: 0-96) respectively. PFS was higher in cases with low DLL4 expression rather than cases with high expressions with no statistically significant differences (P=0.52 and 0.19 respectively). Conclusions: High DLL4 expression in cancer cells was associated with worse OS and DFS than low DLL4 expression.