Molecular Analysis of Vascular Endothelial Growth Factor (VEGF) Receptors in EUS-guided Samples Obtained from Patients with Pancreatic Adenocarcinoma*

Abstract

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.