良性脑膜瘤中自噬小体的超微结构特点及临床意义

Ultrastructural features and clinical significance of autophagosome in benign meningiomas

背景:脑膜瘤是颅内最常见的良性肿瘤之一,临床治疗主要以手术为主,但术后复发率较高,其他治疗方式尚没有确切效果,因此探索新的靶向药物对脑膜瘤治疗具有很好的应用前景,目前自噬现象在良性脑膜瘤中的发病机制尚不十分清楚,仍需要大量实验进行深入研究探讨。目的:探讨自噬在良性脑膜瘤中的超微结构特点及其临床意义。方法:采用光学显微镜诊断脑膜瘤不同分型;采用透射电子显微镜辅助诊断脑膜瘤并进行分型,观察不同分级脑膜瘤细胞胞质中自噬体的超微形态和数量;采用Western blot方法检测不同分级脑膜瘤中自噬相关蛋白Beclin1,LC3的表达水平;应用免疫组织化学染色方法检测脑膜瘤中Vimentin、EMA、PR、S-100和GFAP的表达。结果与结论:入组脑膜瘤176例,男98例,女78例。(1)组织病理学类型CNS WHO 1级良性脑膜瘤共168例,其中脑膜皮型62例,纤维型36例,过渡型58例,血管瘤型12例,CNS WHO 2级透明细胞型4例,非典型性2例,WHO 3级间变性2例;(2)透射电子显微镜观察显示27例WHO 1级脑膜瘤中出现自噬小体,WHO 2级和3级脑膜瘤中未检测到自噬小体;(3)Western blot检测LC3,Beclin1在WHO 1级良性脑膜瘤中高表达,在WHO 2级和3级脑膜瘤中阴性表达;(4)免疫组织化学标志物Vimentin,EMA,PR均有不同程度阳性表达,而S-100和GFAP均阴性表达;(5)结合电镜、免疫组化染色和Western blot结果显示,自噬仅在WHO 1级良性脑膜瘤发生发展过程中发挥重要作用。

BACKGROUND:Meningiomas are one of the most common benign tumors in the intracranial field,and clinical treatment is mainly surgery.However,the postoperative recurrence rate is high,and other treatment modalities do not yet have a definite effect,so the exploration of new targeted drugs is promising for meningioma treatment.At present,the pathogenesis of autophagy in benign meningiomas is not very clear,and a large number of experiments are still needed for in-depth study.OBJECTIVE:To investigate the ultrastructural features and clinical significance of autophagy in benign meningiomas.METHODS:Meningiomas were diagnosed by light microscopy with different subtyping.Diagnosis and typing of meningiomas were aided by transmission electron microscopy,and the ultrastructural morphology and number of autophagosomes in the cytoplasm of meningioma cells of different grades were observed.Western blot assay was used to detect the expression levels of autophagy-related proteins Beclin1 and LC3 in different grades of meningiomas.The altered expression of Vimentin,EMA,PR,S-100 and GFAP in meningiomas was evaluated by immunohistochemical staining.RESULTS AND CONCLUSION:176 meningiomas were identified,including 98 males and 78 females.(1)Histopathological types CNS WHO grade 1 benign meningiomas comprised a total of 168 cases,including 62 cases of meningocortical type,36 cases of fibrous type,58 cases of transitional type,12 cases of angiomatous type,4 cases of CNS WHO grade 2 clear cell type,2 cases of atypical type,and 2 cases of WHO grade 3 anaplastic lesions.(2)Transmission electron microscopy revealed autophagic bodies in 27 cases of WHO grade 1 meningiomas,and no autophagic bodies were detected in WHO grades 2 and 3 meningiomas.(3)LC3 and Beclin1 were highly expressed in WHO grade 1 benign meningiomas by western blot assay and were negatively expressed in WHO grades 2 and 3 meningiomas.(4)The immunohistochemical markers Vimentin,EMA,and PR,were expressed to various degrees,while GFAP and S-100 were negative.(5)A combination of electron microscopy,immunohistochemical staining and western blot assay showed that autophagy only plays an important role in the occurrence and development of WHO grade 1 benign meningiomas.