放射外科治疗脑星形胶质细胞瘤的病理改变对比研究

Pathological features of cerebral gliomas after stereotactic radiosurgery and radiotherapy： a comparative study

目的观察放射外科治疗后星彤胶质细胞瘤的病理、超微结构及肿瘤相关因子Ki-67、血管内皮生长因子（VEGF）、微血管密度（MVD）的变化。方法收集四川省人民医院神经外科自1995年11月至2008年7月间行放射外科治疗后手术切除的脑胶质瘤标本25例（治疗组），同期未接受任何放、化疗原发性脑胶质瘤标本25例作为对照组，2组均由术者留取8例戊二醛固定的电镜标本，观察标本常规病理（HE染色1及肿瘤中心、边缘及瘤周2cm范围内水肿组织超微结构的改变；采刖免疫组化染色检测标本Ki-67、VEGF、MVD的表达。结果治疗组星形细胞瘤坏死程度与肿瘤级别呈正相关fF0．649，P=0．001）；电镜下放疗组肿瘤细胞的细胞器、微血管、血脑屏障分别存肿瘤的中心、肿瘤边缘、瘤周水肿脑组织发生不同程度的变性坏死，而对照组胶质瘤细胞器完整：免疫组化染色结果显示2组标本Ki－67阳性细胞百分率、VEGF蛋白表达和MVD与肿瘤分级均呈正相大天系（P〈0．05），与对照组同级别胶质瘤比较．治疗组Ki-67阳性细胞百分率、MVD较低，差异均有统计学意义（P〈0．05）。结论接受放射外科治疗后肿瘤细胞出现不同程度的变性、坏死、凋亡、微血管血脑屏障破坏，为胶质瘤个体化综合性治疗提供重要佐证。

Objective To study the histopathological changes and ultrastructure features of human gliomas after receiving stereotactic radiosurgery （SRS） and stereotactic radiotherapy （SRT）, and observe the changes of tumor-associated factor Ki-67 level, endothelial growth factor （VEGF） level and microvessel density （MVD）. Methods A comparative, retrospective study of pathological and immunohistochemical changes of 25 glioma specimens without radiotherapy （controls） and 25 patients with glioma received with SRS and SRT （treatment group）, admitted to our hospital from November 1995 to July 2008, were carried out. Eight specimens from both groups, fixed with glutaraldehyde, were chosen for electron microscope observation; the ultrastructure changes in the tumor center, tumor margin and peripheral edema brain tissues in each specimen were observed. Immunohistochemical staining was employed to detect the expressions of Ki-67 and VEGF, and the MVD. And these data were statistically analyzed. Results The square and extent of tumor necrosis and liquation were positively significantly correlated with the tumor grade （r=0.649, P=0.001）. Electron microscope indicated that the organelles, capillaries and blood-brain barrier in the tumor center, tumor margin and peritumoral edema cortex of the treatment group occurred different degrees of brain tissue degeneration and necrosis; while these were without damage in the controls. Immunohistochemistry showed that the protein expression of VEGF, the Ki-67 positive cells, and the MVD in the control group and treatment group were positively correlated with the glioma grade （P〈0.05）. Of the glioma with the same grade, the Ki-67 protein expression and MVD in the treatment group were significantly lower than those in the control group （P〈0.05）. Conclusion SRS and SRT may lead tumor cells to different degrees of degeneration, necrosis, and apoptosis, as well as the three-tier structure damage of capillaries in the blood-brain barrier, which provides a laboratory and theoretical foundation to take individualized comprehensive treatment of different gliomas.