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

J Gastrointestin Liver Dis. 2017 Mar;26(1):51-57. doi: 10.15403/jgld.2014.1121.261.eus.

Abstract

Background and 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.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Aged
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods
  • Female
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Pancreatic Neoplasms / diagnosis*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatitis, Chronic / diagnostic imaging
  • Pancreatitis, Chronic / metabolism
  • Pancreatitis, Chronic / pathology
  • Predictive Value of Tests
  • Prognosis
  • RNA, Neoplasm / genetics
  • Retrospective Studies
  • Sensitivity and Specificity
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • RNA, Neoplasm
  • KDR protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2