KRAS and TP53 mutations are correlated with lower survival rate in resected pancreatic ductal adenocarcinoma

Abstract

Background: Factors responsible for long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC) underwent surgical procedure are poorly understood. Aim of the present study was to clarify the clinical implication of the molecular status of the four genes (KRAS, TP53, p16 and SMAD4), and of other molecular markers, as IDH1 mutation gene, MSI and MGMT promoter methylation status Methods: In this study, 30 PDAC were analyzed. Fifteen patients had a survival rate higher than 53 months from surgery (LS) and 15 patients died for disease before than 24 months from surgery (NLS). The samples were analyzed for KRAS, TP53, NRAS and BRAF mutational status using Next Generation Sequencing Results: NLS group had a higher frequency of cases mutated for KRAS (86.7%) and TP53 (46.7) if compared to LS patients (60.0% p= 0.2148 and 33.3% p= 0.7104, respectively). Intriguingly, when we compared the survival of both “KRAS+TP53” mutated patients with that of “WT/WT” subjects we observed that the survival time of the second group was more than twice higher than the one of “double-mutated samples” (81.0 months vs 35.8 months, p=0.0825) Conclusion: Our data strongly support the fact that KRAS and TP53 mutations identify a subset of PCs with worst behaviour. patients with a KRAS/TP53 mutations had a survival rate less than half if compared with that of KRAS/TP53 wild-type subjects. These molecular markers could be analysed in preoperative material (e.g. EUS-FNA), allowing to provide prognostic information for tailored treatment.