Abstract
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). : characterize the expression of DLL4 in PDAC and ampullary adenocarcinoma (AA), evaluate their correlation with clinicopathologic features and patients’ survival. 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. 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). High DLL4 expression in cancer cells was associated with worse OS and DFS than low DLL4 expression.
Highlights
Pancreatic cancer is currently the 3rd cause of cancer related deaths in USA. 1 It is considered one of the most fatal cancers with a five-year survival rate of 8%. 2 Pancreatic ductal adenocarcinoma (PDAC) is the most common malignant neoplasm of pancreas
Multivariate analysis was done and revealed no statistically significant difference between any of the patients and tumor characteristics and overall survival (OS) and Progression free survival (PFS). This retrospective study was performed on 62 cases including 39 pancreatic ductal adenocarcinoma (PDAC) cases (62.9 %) and 23 AA cases
The current work showed that high Delta-like ligand 4 (DLL4) tumor cell expression was associated with increased tumor size in PDAC but without significant relation and that agrees with Drouillard et al (2016)
Summary
Pancreatic cancer is currently the 3rd cause of cancer related deaths in USA. 1 It is considered one of the most fatal cancers with a five-year survival rate. 2 Pancreatic ductal adenocarcinoma (PDAC) is the most common malignant neoplasm of pancreas. Complete surgical resection of pancreatic cancer is the only treatment option, the 5-year survival of operated cases is only 20%. An evolutionarily conserved intercellular signaling pathway affecting many differentiation processes and cell fate determination during embryonic and postnatal development is known as notch signaling pathway This notch signaling has been shown to play an important role in the development of tumor vasculature and angiogenesis. High DLL4 expression was correlated with poor clinical outcome and overall survival in patients with PDAC. For these reasons, we attempted to study DLL4 expression in both tumor and stromal endothelial cells in all collected cases (PDAC and AA) and its correlation with clinico-pathological data and if there is a correlation between its expression and survival functions of the patients as regards progression free survival (PFS) and overall survival (OS)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
