【作者】 张倩；

【导师】 张红燕；

【作者基本信息】 郑州大学 ， 临床病理学（专业学位）， 2021， 硕士

【摘要】 背景及目的:脑膜瘤是临床常见的原发中枢神经系统肿瘤,占颅内病变的37.0%,好发于女性,男女比例1:2～3。WHO根据组织学特点将脑膜瘤分为3级:大部分为Ⅰ级,良性,其中以上皮型、纤维型、过渡型(或混合型)为主要类型;Ⅱ级、Ⅲ级脑膜瘤生物学行为不稳定,有脑组织侵袭和治疗后复发的特点,以非典型和间变型为主要类型。目前,临床上使用EMA,PR,SSTR2作为脑膜瘤一线诊断的标记物。上皮膜抗原EMA广泛分布于多种上皮细胞及上皮源性肿瘤,蛛网膜帽细胞和脑膜瘤细胞共表达EMA;孕激素受体PR主要应用于诊断乳腺癌、子宫内膜癌和卵巢癌等,脑膜瘤中也存在PR;生长抑素受体SSTR常见于神经内分泌肿瘤,其中SSTR2已发展成为中枢神经系统肿瘤的重要标志物,存在于大多数脑膜瘤中。但这三种标记物常表现出蛋白表达差异导致诊断困难,近年来有研究使用E-cadherin及D2-40作脑膜瘤诊断时,发现二者是辅助诊断有力的标记物。上皮性钙粘附蛋白E-cadherin在组织生长过程中负责细胞连接,脑膜瘤组织中存在E-cadherin表达或缺失;D2-40抗体是针对正常或肿瘤组织中淋巴管内皮的标记物,在正常脑膜及脑膜瘤组织中均可表达。本研究主要探讨脑膜瘤中EMA,PR,SSTR2,E-cadherin及D2-40表达水平以及与组织学分级的相关性,为提高脑膜瘤的诊断正确率提供思路。方法:收集2019年1月-2020年12月在郑州大学第一附属医院病理科诊断为脑膜上皮性肿瘤的病例,共180例,整理其临床资料,主要包括发病部位、患者性别、年龄、临床症状。对肿瘤组织进行常规制片程序处理,并采用免疫组织化学EnVision二步法检测肿瘤组织中EMA,PR,SSTR2,E-cadherin及D2-40的表达水平,经光镜下诊断后按WHO分级和组织学亚型分类。分别比较上述免疫组化指标与临床参数的关系、在不同WHO分级的表达差异和与WHO分级的相关性、SSTR2,E-cadherin,D2-40之间的相关性;在WHO Ⅰ级的上皮型、纤维型、混合型脑膜瘤中的表达差异。结果:1.180例脑膜瘤中,发病率女性高于男性,男性50例,女性130例,男女比例1:2.6;高发年龄段为30-60岁,占65.6%,以额叶、顶叶、颅窝为好发部位。2.脑膜瘤组织学分型以WHO Ⅰ级为主,共134例,其中常见类型为纤维型41例、过渡型39例及上皮型31例。3.在 WHO Ⅰ 级、Ⅱ 级、Ⅲ级脑膜瘤中,EMA,PR,SSTR2,E-cadherin和D2-40阳性表达水平与组织学分级呈负相关(P<0.05);180例脑膜瘤中SSTR2,E-cadherin和D2-40的表达水平之间呈正相关关系(P<0.05)。4.WHO Ⅰ级脑膜瘤中,EMA表达阳性率在上皮型74.2%,过渡型69.2%,其他类型69.6%,明显高于纤维型14.6%;PR表达阳性率分别为上皮型87.1%,其他类型73.9%,高于纤维型26.8%和过渡型46.2%;SSTR2表达阳性率分别为上皮型90.3%,过渡型82.1%,其他类型87.0%,均高于纤维型43.9%;经统计学分析均有显著差异(P<0.05)。E-cadherin和D2-40阳性表达水平在分型比较中无差别(P>0.05)。5.在 WHO Ⅱ 级和Ⅲ级脑膜瘤,联合 EMA+PR+SSTR2+E-cadherin+D2-40检测时诊断脑膜瘤阳性结果为100.0%,明显高于E-cadherin+D2-40的组合80.4%,及EMA+PR+SSTR2检测结果73.9%。经统计学分析差异显著(P<0.05)。结论:1.脑膜瘤中EMA,PR,SSTR2,E-cadherin和D2-40都可表达,均在脑膜瘤临床病理诊断中发挥作用,其中SSTR2,E-cadherin和D2-40的表达水平之间呈正相关,提示三者共同影响脑膜瘤的发生发展过程。2.在纤维型脑膜瘤中联合E-cadherin和D2-40辅助检测更具有诊断价值。3.WHOⅡ级和Ⅲ级脑膜瘤诊断困难时联合EMA+PR+SSTR2+E-cadherin+D2-40共同检测可提高脑膜瘤的诊断正确率。更多还原

【Abstract】 Background and objective:Meningioma is a common tumor of primary central nervous system in clinic,and its incidence accounts for 37.0%of intracranial lesions.The male to female ratio of Meningioma is 1:2～3,which is more common in femal.According to WHO,meningiomas were divided into three grades According to its histological characteristics:most of them are grade I and benign in biological behavior,meningothelial,fibrous(fibroblastic)and transitional(mixed)types are the main variants among them.Grade II and III meningiomas are high grade with unstable biological behavior,which is characterized by brain tissue invasion and recurrence after treatment.Currently,clinicians ues EMA,PR,and SSTR2 as the first-line markers for diagnosis of meningiomas.Epithelial membrane antigen(EMA)is widely exists in many kinds of epithelial cells and epithelial tumors,both arachnoid cap cells and meningioma cells have EMA expression.Progesterone receptor(PR)is generally used to diagnose breast cancer,endometrial cancer and ovarian cancer,etc,and PR is also found in meningioma.somatostatin receptor(SSTR)expresses in neuroendocrine tumors,in which SSTR2 has developed into an important marker of central nervous system tumors and is present in most meningiomas.However,these few immunohistochemistry markers often show differences in protein expression and make it difficult to diagnose.In recent years,there are studies using E-cadherin and D2-40 for the diagnosis of meningioma,it is found that they are effective markers in ancillary diagnosis.Epithelial cadherin has the function of intercellular connection in the procedure of tissue formation and there is expression or absence of E-cadherin in meningioma tissue.D2-40 antibody is a marker targeting lymphatic endothelium in normal or tumor tissues.It is also express in both normal meninges and meningiomas.The main purpose of this experiment was to explore the expression levels of EMA,PR,SSTR2,E-cadherin and D2-40 in meningiomas and their correlation with histological grades,so as to provided points for improving the diagnostic accuracy of meningiomas.Methods:We collected 180 cases of meningeal epithelial tumors which diagnosed in pathology department of the first affiliated Hospital of Zhengzhou University from January 2019 to December 2020.Their clinical data were sorted out including the location of the disease,the patient’s gender,age and clinical symptoms.The tumor tissue was treated into hematoxylin-eosin stained sections,detected the expression level of EMA,PR,SSTR2,E-cadherin and D2-40 in tumor tissue by immunohistochemical EnVision two-step method.After diagnosis under light microscope,these cases was classified in accordance with WHO grade and histological subtype.Then compare the relationship between the above-mentioned markers and clinical dates,the expression differences in different WHO grades and the correlation with WHO grades,the correlation between SSTR2,E-cadherin,and D2-40,as well as the expression differences among meningothelial,fibrous and transitional patterns of WHO grade Ⅰ.Results:1.Among the 180 cases of meningioma,the incidence rate of female was higher than that of male,50 cases of male and 130 cases of female,the ratio of male to female was 2.6;the generation of high incidence was 30-60 years old,accounting for 65.6%,with frontal lobe,parietal lobe and cranial fossa as the most common sites;histological classification was mainly WHO grade I,a total of 134cases.2.The histological classification of meningioma is mainly WHO I grade,with a total of 134 cases,of which common patterns are fibrous(n=41),transitional(n=39)and meningothelial(n=31).3.In WHO grade Ⅰ,Ⅱ and Ⅲ meningiomas,the positive expression levels of EMA,PR,SSTR2,E-cadherin and D2-40 were negatively correlated with histological grade(P<0.05).There was a positive correlation between the expression of SSTR2,E-cadherin and D2-40 in meningiomas(P<0.05).4.In WHO grade I meningiomas,the positive rates of EMA expression in meningothelial type,transitional type and other types were 74.2%,69.2%and 69.6%,respectively,which were significantly higher than that in fibrous type(14.6%);the positive rate of PR expression was 87.1%in meningothelial type and 73.9%in other types,which were higher than that in fibrous type(26.8%)and transitional type(46.2%).The positive rate of SSTR2 expression in meningothelial type,transitional type and other types was 90.3%,82.1%and 87.0%,respectively,which were higher than that in fibrous type(P<0.05).The positive expression levels of E-cadherin and D2-40 had no difference in comparison of histological subtypes(P>0.05).5.In grade WHO Ⅱ and Ⅲ meningiomas,the positive rate of meningioma diagnosed by combined EMA+PR+SSTR2+E-cadherin+D2-40 test was 100.0%,which was significantly higher than that of E-cadherin+D2-40 combination(80.4%)and EMA+PR+SSTR2 test result(73.9%).The difference was obvious after statistical analysis(P<0.05).Conclusion:1.EMA,PR,SSTR2,E-cadherin,and D2-40 all express in meningioma tissue,which play an important role in the clinicopathological diagnosis of meningioma.Among them,the expression levels of SSTR2,E-cadherin and D2-40 are positively correlated,suggesting that they jointly affect the occurrence and development of meningiomas.2.The combination of E-cadherin and D2-40 has more diagnostic value in fibrous meningioma.3.The combined detection of EMA+PR+SSTR2+E-cadherin+D2-40 can improve the diagnostic accuracy of meningiomas when the diagnosis of WHO gradeⅡ and Ⅲ meningioma is difficult.更多还原