诱导型一氧化氮合酶在反应性及肿瘤性星形胶质细胞中的表达

目的:探讨诱导型一氧化氮合酶(iNOS)、突变型p53及VEGF在反应性及肿瘤性星形胶质细胞中的表达及其在星形胶质细胞瘤发生发展、血管形成中的作用。方法:应用组织芯片及免疫组织化学技术检测12例正常脑组织、49例星形细胞反应性增生、49例低级别(I-II级)及50例高级别(III-IV级)星形胶质细胞瘤中iNOS、突变型p53、VEGF表达情况。结果:在正常脑组织中三者均为阴性表达;从星形细胞反应性增生组到高级别星形细胞瘤组,三者的阳性表达率均呈升高趋势,分别为:iNOS:28.89%(13/45),57.75%(27/47),81.63%(40/49);p53:23.81%(10/42),53.66%(22/41),79.55%(35/44);VEGF:22.73%(10/44),44.19%(19/43),69.77%(30/43),并且三者在星形细胞反应性增生组及低级别星形胶质细胞瘤组中的表达差异显著(P<0.05);各实验组中iNOS与p53表达水平一致性较好,具有明显的相关性(P<0.05);而iNOS与VEGF在低级别及高级别星形胶质细胞瘤组中表达水平具有较好的一致性及明显的相关性(P<0.05),在反应性增生组表达无相关性(P>0.05)。结论:iNOS、突变型p53及VEGF的过表达是胶质瘤发生的早期分子生物学事件,三者相互作用共同促进星形胶质细胞瘤的发生发展及血管的形成;单一或联合检测可能有助于星形细胞反应性增生及低级别星形细胞瘤的鉴别诊断。

The expression of inducible nitricoxide synthase(iNOS) in reactive astrogliosis and astrocytoma

Objective:To investigate the expression of inducible nitric oxide synthase (iNOS),mutation-type p53 and vascular endothelial growth factor(VEGF) in reactive astrogliosis and astrocytoma, and explore the relationships among expression of these markers and tumorigenesis and angiogenesis. Methods: Immunonhistochemistry and tissue microarray technique were used to determine the expression of the three biomarkers in 49 cases of astrocytes proliferation, 49 cases of low-grade astrocytomas,and 50 cases of high-grade astrocytomas;meanwhile,12 cases of normal brain tissues were used as controls. Results: The expression of the three biomarkers was negative in the control group, but stepwise increase of the positive rate of expression of them was found from reactive astrogliosis, through low-grade astrocytoma to high-grade astrocytoma, iNOS: 28.89%(13/45),57.75%(27/47),81.63%(40/49); p53: 23.81% (10/42),53.66% (22/41),79.55% (35/44);VEGF: 22.73% (10/44),44.19% (19/43),69.77% (30/43), respectively; furthermore, the expressions of them between the reactive astrogliosis group and low-grade astrocytoma group all were significantly different. In low-grade and high-grade astrocytomas, the expression of iNOS positively correlated with p53 and VEGF, but in reactive astrogliosis group, no association was found between iNOS and VEGF. Conclution: iNOS,p53 and VEGF may play a role in malignant changes during astrocytic tumorigenesis and angiogenesis; The overexpression of them may develop in the earlier stage of tumorigenesis and they may have potential value in the diagnosis of reactive astrocytes and low-grade astrocytomas.