Background & Aims: Vascular endothelial growth factor (VEGF) and its receptors (VEGF-R1 and VEGF-R2) are the most important angiogenesis stimulating factors in pancreatic cancer. This study aims to assess VEGF-R1 and VEGF-R2 gene expression in EUS-FNA samples and identify prognostic markers in pancreatic adenocarcinoma.Methods. This was a retrospective study of prospectively collected data of 88 consecutive patients, with clinical and imaging suspicion of pancreatic neoplasms, based on samples obtained through endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).Results. EUS had an accuracy of 93.2% for the diagnosis of pancreatic cancer. Based on real-time qPCR analysis, VEGF-R1 and VEGF-R2 expressions were present in 90% and 65% of the analysed malignant samples, respectively; 89% of the patients died during the study, with a median survival rate of only 9 months. The survival was correlated with the initial stage and with the presence of VEGF-R1 and VEGF-R2 gene expression. We found that there are significant correlations between death/survival and T stage, N stage, resectability status, VEGF-R1, VEGF-R2 and VEGF-R1/VEGF-R2 coexpression. Using a Cox model regression our study demonstrates that VEGF-R1/VEGF-R2 coexpression might be considered as a poor prognostic factor in pancreatic cancer.Conclusions. EUS is a very effective technique for the diagnosis and staging of pancreatic adenocarcinoma in patients with clinical and imaging suspicion of pancreatic neoplasm, with an accuracy of 93.2%. Furthermore, the role of molecular analysis of EUS-guided FNA samples was established by the assessment of VEGF-R1, VEGF-R2 gene expression, which might be considered prognostic markers in pancreatic cancer.Abbreviations: cDNA: deoxyribonucleic acid concentration; CE-EUS: contrast enhanced endoscopic ultrasound; CT: computed tomography; EUS: endoscopic ultrasound; EUS–FNA: endoscopic ultrasound guided fine needle aspiration; IHC: immunohistochemistry; MRI: magnetic resonance imaging; qRT–PCR: quantitative real time polymerase chain reaction; RNA: ribonucleic acid; VEGF: vascular endothelial growth factor; VEGF-R1: vascular endothelial growth factor receptor 1; VEGF-R2: vascular endothelial growth factor receptor 2.

Pancreatic disorders have a high prevalence worldwide. Despite the fact that screening methods became more effective and the knowledge we have nowadays about pancreatic diseases has enhanced, their incidence remains high. Our purpose was to determine whether single nucleotide polymorphism (SNP) of VEGFR-2/KDR (vascular endothelial growth factor receptor 2/kinase insert domain receptor) influences susceptibility to develop pancreatic pathology. Genomic DNA was extracted from blood samples collected from patients diagnosed with acute pancreatitis (n = 110), chronic pancreatitis (n = 25), pancreatic cancer (n = 82) and healthy controls (n = 232). VEGFR-2 (KDR) 604A>G (rs2071559) polymorphism frequency was determined with TaqMan allelic discrimination assays. Statistical assessment was performed by associating genetic polymorphism with clinical and pathological data. In both pancreatic disorders and healthy control groups the polymorphism we studied was in Hardy-Weinberg equilibrium. Association between increased risk for pancreatic disorders and studied polymorphism was statistically significant. KDR 604AG and AG + GG genotypes were more prevalent in acute pancreatitis and pancreatic cancer patients than in controls. These genotypes influence disease development in a low rate. No association was found between chronic pancreatitis and KDR 604AG and AG + GG genotypes. In Romanian cohort, we found an association between the KDR 604A→G polymorphism and acute pancreatitis and pancreatic cancer. Carriers of the -604G variant allele were more frequent among acute pancreatitis and pancreatic cancer than among controls, suggesting that KDR 604G allele may confer an increased risk for these diseases. In the future, more extensive studies on larger groups are necessary, in order to clarify the role of VEGFR2 polymorphisms in pancreatic pathology.

The connection between central obesity and the development and metastasis of various visceral tumors is largely accepted and one of the main causes seems to be the local synthesis of proangiogenic molecules. Progranulin (PRG), recently identified as an adipokine, is a novel pleiotropic growth factor acting on the proliferation and development of fast-growing epithelial cells, cancer cells, and also a proangiogenic factor whose expression is induced in activated endothelial cells. One of the molecules that seems to trigger the angiogenic activity of PRG is vascular endothelial growth factor (VEGF). Two groups of human subjects were considered and adipose tissue was processed for an immunohistochemical and morphometric study after surgery for abdominal tumoral or non-tumoral pathology. The presence of PRG in adipose pads of the omentum was analyzed and its association with VEGF, CD34 and collagen IV in tumoral and non-tumoral visceral pathology was examined. The results showed that PRG but not VEGF expression was upregulated in adipose tissue in tumoral visceral pathology. In conclusion, the involvement of the proangiogenic activity of PRG and VEGF in adipose tissue under tumor conditions may be dependent on the visceral tumor type.