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VASCULAR ENDOTHELIAL GROWTH FACTORS AND CD34 EXPRESSION CAN IMPLEMENT NICE (NBI INTERNATIONAL COLORECTAL ENDOSCOPIC) CLASSIFICATION IN COLORECTAL POLYPOID LESIONS DIAGNOSIS?
Cesare Ruffolo*1, Francesco Ferrara2, Elisabetta Trevellin3, Ivana Cataldo4, Andromachi Kotsafti5, Caterina Fornasier1, Anna Pozza1, Marta Campo Dell'Orto4, Imerio Angriman5, Angelo Paolo Dei Tos4, Romeo Bardini5, Marco Massani1, Marco Scarpa5
1Department of Surgery, Azienda ULSS2 Marca Trevigiana, Treviso, Treviso, Italy; 2Gastroenterology unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy; 3Department of Medicine, Endocrine-Metabolic Laboratory, University of Padova, Padova, Italy; 4Pathology unit, Azienda ULSS2 Marca Trevigiana, Treviso, Italy; 5General Surgery unit, University Hospital of Padova, Padova, Italy

Background
Neoangiogenesis is a hallmark of carcinogenesis progression. Vascular endothelial growth factor (VEGF) is a subfamily of growth factors involved in angiogenesis and CD34+ cells are normally found in endothelial progenitor cells and endothelial cells of blood vessels. Colonic adenomatous polyps may not always be completely removable endoscopically and a preoperative diagnosis is still necessary. The aim of the study was to evaluate whether VEGF-A, VEGF-C and CD34 mRNA expression along colorectal carcinogenesis steps can implement NICE (NBI International Colorectal Endoscopic) classification in the diagnosis of malignancy in colorectal polypoid lesions.
Methods
Seventy-one subjects with colonic adenoma or cancer who underwent screening narrow band imaging (NBI) colonoscopy were prospectively enrolled. Polyps were classified according to NICE classification. Real time RT-PCR for VEGF-A, VEGF-C and CD34 mRNA expression was performed. Non-parametric statistics, ROC curves analysis and logistic multiple regression analysis were used.
Results
VEGF-A and CD34 mRNA expression was significantly higher in sessile adenomas than in polypoid ones (p<0.001 and p=0.01, respectively). VEGF-A, VEGF-C and CD34 mRNA expression was significantly higher in adenocarcinoma than in adenoma (p=0.01, p=0.01 and p=0.01, respectively). The accuracy of VEGF-A, VEGF-C and CD34 mRNA expression for prediction of malignancy was 0.79 (95%CI=0.65-0.90), 0.81 (95%CI=0.66-0.91), 0.80(95%CI=0.65-0.90), respectively, while the accuracy of NICE classification was 0.85 (95%CI=0.72-0.94). The determination coefficient R2, that indicates the amount of variability explained by a regression model, for NICE classification alone was 0.24 (p<0.001). A regression model that included NICE classification and VEGF-C mRNA expression showed a R2=0.39 as well as a model including NICE classification and CD34 mRNA levels.
Conclusions
This study demonstrated that VEGF-C and CD34 mRNA levels might be useful to stratify colorectal polyps in different risk of progression classes implementing the accuracy of NICE classification. Studies on in vivo detection of these markers are warranted.


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