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Article 11, 1/2017

ORIGINAL PAPER

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

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Mădălin Ionuț Costache1,2, Sevastița Iordache1, Cornelia Alexandra Costache3, Ene Dragos4, Alexandru Dragos5, Adrian Săftoiu1,6

1) Dept. of Gastroenterology, Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova;
2) Dept. of Radiology, Craiova County Hospital, Craiova;
3) Dept. of Neurology, University of Medicine and Pharmacy Craiova;
4) Dept. of Surgery, Carol Davila University of Medicine and Pharmacy, Bucharest;
5) Dept. of Statistics and Medical Informatics, University of Medicine and Pharmacy Craiova, Romania
6) Dept. of Endoscopy, Gastro-Unit, Copenhagen University Hospital Herlev, Denmark

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.261.eus

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.
Key words: pancreatic cancer – EUS-FNA – VEGF-R1 – VEGF-R2 – prognostic factors.
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.