摘要
目的探讨胶质瘤血管内皮生长因子(VEGF)、血管内皮生长因子-C(VEGF-C)和血管内皮生长因子受体-3(VEGFR-3)表达变化,以及对肿瘤细胞增殖和间质血管生成的影响。方法收集2000-2009年手术切除WHO Ⅰ～Ⅱ级、Ⅲ级和Ⅳ级胶质瘤标本各20例,采用组织微阵列技术及免疫组织化学染色(SPAB法)观察不同级别胶质瘤组织中VEGF、VEGF-C、VEGFR-3和Ki-67抗原的表达及CD31阳性血管密度。结果 60例胶质瘤组织中肿瘤细胞及间质血管内皮细胞VEGF、VEGF-C和VEGFR-3阳性表达率分别为88.33%(53/60)和100%(60/60)、100%(60/60)和16.67%(10/60)、100%(60/60)和21.67%(13/60),不同级别组间差异均无统计学意义(P>0.05)。Ⅰ～Ⅱ级、Ⅲ级及Ⅳ级组的VEGF阳性肿瘤细胞密度分别为(17.65±9.00)、(37.30±18.54)和(83.40±22.98)个/0.05 mm^2;VEGF-C阳性肿瘤细胞密度为(38.00±17.82)、(79.30±5.23)和(102.00±1 3.07)个/0.05 mm^2;VEGFR-3阳性血管密度(3 65±2.01)、(10.50±3.98)和(14.60±7.29)血管数/4 HF;Ki-67抗原阳性肿瘤细胞密度(9.30±3.48)、(31.15±9.44)和(60.15±13.60)个/0.05 mm^2;CD31阳性血管密度(6.75±2.24)、(10.35±2.98)和(14.30±3.51)血管数/4 HF,各组之间以上5种指标比较差异均有统计学意义(P<0.05或P<0.01),且彼此间均呈显著性正相关关系(r=0.663～0.910,P<0.01)。结论胶质瘤细胞普遍过表达VEGF和VEGF-C,而胶质瘤间质血管内皮细胞则普遍过表达VEGFR-3,三者表达水平均随着肿瘤级别的升高而相应增加;由此形成的旁分泌环通过诱导问质血管生成促进肿瘤细胞增殖,在胶质瘤的发生、发展过程中起着重要作用。
Objective To explore the changes of vascular endothelial growth factor （VEGF）, vascular endothelial growth factor-C （VEGF-C） and vascular endothelial growth factor receptor-3 （VEGFR-3） expression and their impacts on tumor cell proliferation and interstitial angiogenesis in gliomas Methods The specimens of 20 cases of WHO grade Ⅰ -Ⅱ, 20 cases of grade Ⅲ and 20 cases of grade Ⅳ gliomas were collected from Department of Neurosurgery in Tianjin Medical University General Hospital during the period from 2000 to 2009. The expressions of VEGF, VEGF-C, VEGFR-3 and Ki-67 as well as the density of CD31 positive vessels were detected in 60 gtiomas with different grades of malignancy by of tissue microarray and im mu nohistochemistry. Results in the tumor cells and vascular endothelial cells of 60 patients with gliomas, the positive rate of VEGF, VEGF - C and VEGFR - 3 88.33% （53/60） and 100% （60/60）, 100% （60/60） and 16.67% （10/60）, and 100% （60/60） and 21.67% （13/60） of tumor cells, respectively. No significant differences were seen among groups in different grades （P 〉 0.05, for all）. In grade I -Ⅱ, grade Ⅲ and grade Ⅳ gliomas, the density of VEGF positive tumor cells was （17.65 ± 9.00）, （37.30 ± 18.54） and （83.40 ± 22.98） positive cell number/0.05 mm2, the density of VEGF-C positive tumor cells was （38.00 ± 17.82）, （79.30 ± 5.23） and （102.00 ± 13.07） positive cell numbcr/O.05 mm2, the density of VEGFR-3 positive vessels was （3.65 ± 2.01）, （10.50 ± 3.98） and （14.60 ± 7.29） positive vessel number/4 HF, the density of Ki-67 positive tumor cells was （9.30 ± 3.48）, （31.15 ± 9.44） and （60.15 ± 13.60） positive cell number/0.05 mm2, and CD31 positive microvessels was （6.75 ± 2.24）, （10.35 ± 2.98） and （14.30 ± 3.51） positive vessel number/4 HF, respectively. The differences of each parameter mentioned above were all significant among the groups in different grades （P 〈 0.05 or P 〈 0.01）, and they were positively correlated with each other （r = 0.663-0.910, P〈0.01）. Conclusion Over-expression of VEGF and VEGF-C was seen in glioma cells, and VEGFR-3 was also over-expressed in interstitial vascular endothelial cells. Their expression levels increased along with the grade of malignancy. The paracrine loops composed by them can induce interstitial angiogenesis and tumor cell proliferation, and thereby play a crucial role in the occurrence and progression of gliomas.
出处
《中国现代神经疾病杂志》
CAS
2010年第4期473-478,共6页
Chinese Journal of Contemporary Neurology and Neurosurgery
基金
天津市自然科学基金资助项目(项目编号:013616411)
天津市科技支撑计划重点项目(项目编号:07ZCKFSF00800)
天津市高等学校科技发展基金计划项目(项目编号:20060202)
