Ni Hai-chun, Sun Fu-hai, Piao Yue-shan, Ma Xiao-li, Lu De-hong
Department of Pathology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Zhonghua Bing Li Xue Za Zhi. 2012 Jun;41(6):391-5. doi: 10.3760/cma.j.issn.0529-5807.2012.06.007.
To investigate the expression of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 in refractory epilepsy associated malformation of cortical development (MCD) tissues.
A total of 43 cases of refractory epilepsy were involved in the study, and all the patients were treated in Xuanwu Hospital during 2005 - 2008, including focal cortical dysplasia type IIa (11 cases) and type IIb (11 cases), tuberous sclerosis complex (10 cases) and ganalioglioma (11 cases), and other 12 cases were used as control. These cases were divided into 7 study groups and immunohistochemical EnVision method was used. To detect the location and intensity of TSC1, TSC2, p-mTOR, p-4E-BP1, p-p70S6K and p-S6 expression in every group. Then the Image-Pro Plus 6.0 image processing and analysis software were used to measure the number, area, integrating absorbance (IA) of positive cells in every samples. The statistical software SPSS 16.0 was used to analyze the data.
The immunolocalization of TSC1 and TSC2 was similar. It could be observed the expression of various levels in the cytoplasm of dysmorphic neurons, balloon cells, giant cells, ganglioglioma cells and normal neurons. TSC1 staining in normal neurons was more notably than others but TSC2 staining in giant cells was weaker than other samples. p-mTOR mainly presented in giant cells, which could also be observed in astrocyte. P-4E-BP1 presented in the cytoplasm and nuclear membrane of balloon cells, giant cells and ganglioglioma cells, the staining of giant cells was stronger than balloon cells, but their staining were weaker than ganglioglioma cells. P-p70S6K mainly expressed in giant cells and less commonly presented in balloon cells. P-S6 typically presented in all abnormal glioneuronal cells and it nearly did not present in the normal neurons of N-CTX group.
PI3K pathway, at least in part, involves in the occurrence of MCD, and may play an important role in the pathogenesis.
探讨结节性硬化复合物1（TSC1）、结节性硬化复合物2（TSC2）、磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）、磷酸化真核起始因子4E结合蛋白1（p-4E-BP1）、磷酸化核糖体蛋白S6激酶（p-p70S6K）和磷酸化核糖体蛋白S6（p-S6）在难治性癫痫伴皮质发育畸形（MCD）组织中的表达情况。
本研究共纳入43例难治性癫痫患者，所有患者均于2005年至2008年在宣武医院接受治疗，其中包括IIa型局灶性皮质发育不良（11例）、IIb型局灶性皮质发育不良（11例）、结节性硬化症（10例）和节细胞胶质瘤（11例），另外12例作为对照。将这些病例分为7个研究组，采用免疫组织化学EnVision法，检测每组中TSC1、TSC2、p-mTOR、p-4E-BP1、p-p70S6K和p-S6表达的部位及强度。然后使用Image-Pro Plus 6.0图像处理与分析软件测量每个样本中阳性细胞的数量、面积、积分吸光度（IA）。采用统计软件SPSS 16.0对数据进行分析。
TSC1和TSC2的免疫定位相似。在发育异常的神经元、气球样细胞、巨细胞、节细胞胶质瘤细胞及正常神经元的细胞质中均可观察到不同程度的表达。正常神经元中TSC1染色比其他细胞更明显，但巨细胞中TSC2染色比其他样本弱。p-mTOR主要出现在巨细胞中，在星形胶质细胞中也可观察到。P-4E-BP1出现在气球样细胞、巨细胞和节细胞胶质瘤细胞的细胞质及核膜中，巨细胞的染色强于气球样细胞，但其染色弱于节细胞胶质瘤细胞。P-p70S6K主要表达于巨细胞，较少出现在气球样细胞中。P-S6典型地出现在所有异常的神经胶质神经元细胞中，在N-CTX组的正常神经元中几乎不出现。
PI3K通路至少部分参与了MCD的发生，可能在其发病机制中起重要作用。
