摘要目的 分析哺乳动物雷帕霉素靶蛋白(mTOR)和血管内皮生长因子(VEGF)在胃肠胰神经内分泌肿瘤(GEP-NEN)组织中的表达及其相关性和临床意义.方法 收集1995年10月至2012年12月经病理确诊的114份GEP-NEN石蜡组织标本,采用免疫组织化学EnVision法检测标本中mTOR和VEGF的蛋白表达情况.采用卡方检验比较患者各临床病理因素间的mTOR和VEGF蛋白的表达差异.采用Spearman相关分析检测mTOR和VEGF蛋白表达的相关性.生存分析采用Kaplan-Meier 法,行Log-rank检验.结果 mTOR和VEGF蛋白在GEP NEN组织中的阳性表达率分别为66.7％(76/114)和71.1％(81/114).mTOR和VEGF的蛋白表达与GEP-NEN患者的性别、年龄、肿瘤功能状态、肿瘤发生部位、肿瘤分级分类和有否远处转移均无关(P均＞0.05).mTOR和VEGF蛋白在GEP-NEN组织中的共同表达率为51.8％(59/114).mTOR和VEGF蛋白的表达呈正相关(r=0.205,P=0.029).82例随访患者中,mTOR阳性和阴性的平均生存时间分别为8.3和7.9年,差异无统计学意义(x2=0.201,P=0.654);VEGF阳性和阴性的平均生存时间分别为9.6和5.9年,差异有统计学意义(x2 =4.415,P=0.036).肿瘤分级为G1、分类为神经内分泌瘤和无远处转移的VEGF阳性表达患者较阴性表达患者生存期延长(11.8年比7.3年,x2=5.349,P=0.021;11.2年比6.8年,x2=6.375,P=0.012;11.2年比7.2年,x2=4.630,P=0.031).结论 mTO R和VEGF蛋白在不同部位、分级、分类的神经内分泌肿瘤中均高表达,两者表达呈正相关.VEGF阳性表达的GEP-NEN患者预后较好.

abstractsObjective 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.