Expression and its clinical significance of mammalian target of rapamycin and vascular endothelial growth factor in gastroenteropancreatic neuroendocrine neoplasm

Abstract

Objective To explore the expression,correlation and clinical significance of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN).Methods From October 1995 to December 2012,the paraffin tissue specimens of 114 pathological diagnosed GEP-NEN were collected.The expressions of mTOR and VEGF at protein level were detected with EnVision immunohistochemical staining method.Chi-square test was performed to compare the differences in the expressions of mTOR and VEGF among every clinicopathological factors of patients.Spearman's correlation analysis was used to find out the correlation between the expressions of mTOR and VEGF.Kaplan Meier method and Log-rank test were implemented for survival analysis.Results The overall positive expression rates of mTOR and VEGF in GEP-NEN tissues were 66.7％ (76/114) and 71.1％ (81/114),respectively.The expressions ofmTORand VEGF at protein level were not correlated with gender,age,functional status of tumor,location of tumor,grading and classification of tumor and distant metastasis (all P＞0.05).The co-expression rate of mTOR and VEGF in GEP-NEN tissues was 51.8％ (59/114).The expression of mTOR was positively correlated with the expression of VEGF at protein level (r=0.205,P=0.029).Among 82 followed-up patients,the mean survival time of patients with mTOR positive or negative expression was 8.3 and 7.9 years,and respectively,and there was no statistical significance (x2 =0.201,P=0.654).The mean survival time of patients with VEGF positive or negative expression was 9.6 and 5.9 years,respectively,and the difference was statistically significant (x2 =4.415,P=0.036).Among the patients with G1 grading tumor,classified as neuroendocrine tumor and without distant metastasis,the survival time of patients with positive VEGF expression was longer than that of patients with negative VEGF expression (11.8 years vs 7.3 years,x2 =5.349,P=0.021; 11.2 years vs 6.8 years,x2=6.375,P=0.012; 11.2 years vs 7.2 years,x2 =4.630,P=0.031).Conclusions mTOR and VEGF proteins are highly expressed in GEP-NEN with different location,grading and classification.The expression of them is positively correlated.The prognosis of GEP-NEN patients with positive VEGF expression is better. Key words: Neuroendocrine tumors; Gastroenteropancreatic; mTOR; Vascular endothelial growth factor