【作者】 袁东风；

【导师】 刘凡英；

【作者基本信息】 山东大学 ， 外科学， 2012， 硕士

【摘要】 背景和目的：胸腺上皮肿瘤(thymus epithelial tumor, TET)是一种起源于胸腺上皮细胞的肿瘤,多发生于前纵膈,约占成人纵隔肿瘤的20%,是最常见的纵隔肿瘤之一。D2-40最早发现于肾小球的足突细胞膜,属于Ⅰ型粘液样跨膜糖蛋白。它虽然特异性表达于淋巴管内皮,但还在许多正常细胞和肿瘤细胞中表达。采用D2-40的免疫组织化学法检测淋巴管,被用于评估肿瘤及瘤周微淋巴管密度与淋巴结情况和预后的关系。在许多恶性肿瘤细胞中发现了D2-40的表达,如血管瘤、恶性间皮瘤、中枢系统肿瘤、生殖细胞肿瘤和鳞状细胞癌等。D2-40在胸腺上皮肿瘤中表达的研究较少,本研究采用免疫组织化学染色方法,检测TET组织中D2-40的表达情况,评估D2-40在TET侵袭和转移中的意义。方法：收集1992年1月至2006年1月在山东省立医院胸外科进行手术切除并经病理证实为胸腺瘤和胸腺癌的160例石蜡标本。其中胸腺瘤119例,胸腺癌41例。取20例正常小儿胸腺和20例成人萎缩胸腺为正常对照,均取自行心外科手术患者。通过免疫组织化学S-P法检测D2-40在160例不同类型及分期的胸腺上皮肿瘤,以及40例正常胸腺组织中的表达。使用SPSS17.0软件建立数据库来进行分析。D2-40的表达情况分析采用卡方检验,生存分析采用Kaplan-Meier法,生存差异采用Log-rank法,独立的预后因素分析采用Cox回归模型。当P<0.05认为差异有统计学意义。结果：1.正常对照组：共40例,小儿胸腺20例,年龄0.8～15岁,平均年龄5.1±3.4岁；成人萎缩胸腺20例,年龄23～48岁,平均年龄32.5±6.8岁。TET组：共160例,年龄15～78岁,平均年龄48.4±12岁。2.病理组织学特征：按照2004年WHO最新病理组织学分型标准,其中A型10例,AB型24例,B1型26例,B2型42例,B3型12例,B2/B3混合型5例,胸腺癌41例。按照Masaoka分期,Ⅰ期51例,Ⅱ期32例,Ⅲ期58例,Ⅳa期5例,Ⅳb期14例。肿瘤直径范围从2cm到20cm,中位数为7cm。其中36例肿瘤直径小于5am,24例直径大于10cm。肿瘤大小与临床分期间关系有统计学意义(P=0.017),而与病理组织学分型间关系无统计学意义(P=0.098)。3.D2-40的表达情况：D2-40在正常胸腺和TET中的表达率分别是20%(8/40)、58.8%(66/160),二者之间的差异有统计学意义(P=0.013)。在非侵袭性TET及侵袭性TET中的表达率分别是5.9%(3/51)、63.6%(63/99)差异有统计学意义(P<0.01)。D2-40的表达与年龄相关(P<0.001),而与性别、肿瘤大小和是否并发重症肌无力无关。4.生存分析：160例TET患者5年生存率是63%,D2-40表达阳性与阴性的5年生存率分别是32%、90%(P<0.001)。与预后有关因素的Kaplan-Meier生存分析结果表明预后与临床分期(P<0.001)、病理组织学分型(P<O.001)、肿瘤大小(P=0.005)及D2-40的表达(P<0.001)均相关。Cox多因素回归分析结果表明临床分期(P=O.002,相对危险度为7.055)、病理组织学分型(P=0.004,相对危险度为6.755)和D2-40的表达(P=0.008,相对危险度为3.069)是影响预后的独立因素。结论：1.正常胸腺组织和TET组织中均可见D2-40的阳性表达,但TET组织中的表达明显高于正常胸腺组织。2.随Masaoka分期增高,TET组织中D2-40表达阳性率和强度相应增高,也就是说D2-40的表达随着TET的侵袭性增强而增强。3.D2-40的表达与TET患者年龄、临床分期、组织学分型相关,而与性别、肿瘤大小和是否并发重症肌无力无关。4.Cox多因素回归分析结果表明临床分期、病理组织学分型和D2-40的表达是影响预后的独立因素。5.应用免疫组化S-P法检测D2-40的表达情况,可以评估和预测TET侵袭和淋巴转移的潜在可能,并为进一步开展TET的研究和治疗提供依据。更多还原

【Abstract】 Background and objective:Thymic epithelial tumor (TET) is a kind of originated in the thymus epithelial cell tumor, which is the most common anterior mediastinum of adult, as accounting for about20%of the adult mediastinal tumor. It is one of the most common mediastinal tumor. Podoplanin, originally detected on the surface of podocytes, belongs to the family of type-1transmembrane sialomucin-like glycoproteins. Although specific for lymphatic vascular (LV) endothelium, podoplanin is expressed in a wide variety of normal and tumor cells. D2-40in lymphatic endothelial cell (LECs) was used in many studies to evaluate the LV microvascular density (LVMD) in peritumoral and tumoral areas, and to correlate LVMD with lymph node status and prognosis. D2-40expression was found in tumor cells of various types of cancer, such as vascular tumors, malignant mesothelioma, tumors of the central nervous system (CNS), germ cell tumors and squamous cell carcinomas. There are few studies about the expression of D2-40in the thymic epithelial tumor. Immunohistochemical method was used to detect the expression of D2-40in TET and their putative significance in the invasion and metastasis, to further explore the possible mechanism of metastasis of TET.Methods:Collect January1992to January2006in shandong province hospital operations to remove thoracic surgery and confirmed by pathology for thymic lesion and160cases of thymic carcinoma paraffin specimens. All of cases contions119thymus tumor and41thymic carcinoma. Take20cases of normal children the thymus and20adults atrophy the thymus for normal controls, which take from heart surgery patients. Detect D2-40by the immunohistochemical S-P method in160cases of different types and staging TET, and40patients with normal thymus tissue of expression. Use SPSS17.0software based on the database to be analyzed. D2-40expression used chi-square test. Kaplan-Meier method was performed to calculate the survival rate. Log-rank method was performed to compare the survival difference between the patients with and without D2-40expression. Cox regression multivariate analysis was performed to determine independent prognostic factor. Differences were considered significant when the P value was less than0.05.Results:1. The normal group:40cases, the ages of the children thymus20cases patients ranged from0.8tol5years, with an average of55.1±3.4years. The ages of the adult atrophy thymus20case patients ranged from23to48years, with an average of32.5±6.8years.TET groups:The ages of the160patients ranged from15to78years, with an average of48.4±12years.2. The pathological and histological characteristics:The tumors consisted of10type A,24type AB,26type B1,42type B2,12type B3,5combined thymomas and41according to the World Health Organization histological classification system and of51stage Ⅰ,32stage Ⅱ,58stage Ⅲ,5stage IVa, and14stage IVb thymomas according to the Masaoka staging system. The tumors ranged in size from2to20cm in maximum dimension (median,7cm). Thirty-six tumors were smaller than5cm, and twenty-four tumors were larger than10cm. There was a statistically significant association between tumor size and clinical stage (P=0.017), whereas no association was established between tumor size and histological subtype (P=0.098).3. D2-40expression:D2-40in normal the thymus and the TET expression rate respectively were20%(8/40),58.8%(66/160), and the difference is statistically significant (.P=0.013). In the noninvasive TET and aggressive in the TET expression rate respectively were5.9%(3/51),63.6%(63/99), and the difference was statistically significant (P<0.01). D2-40of the expression and the relevant age (P<0.001). Patient gender, tumor size, and myasthenia gravis were not associated with D2-40expression, 4. Survival analysis:Actuarial5-years survival of160TET cases was63%. Actuarial5-years survival of D2-40express positive and negative groups were32%,90%(P<0.001). The Kaplan-Meier survival curves according to the prognostic factors are shown that statistically significant differences were observed in the clinical stages (P<0.001), pathology organization credits type (P<0.001), tumor size (P=0.005) and D2-40expression (P<0.001). The results of Cox regression multivariate analysis conformed that the clinical stage (P=0.002, relative risk7.055), pathology organization credits type (P=0.004, relative risk6.755) and D2-40expression (P=0.008, relative risk3.069) was independent factors.Conclusions:1. Normal thymus organization and thymic epithelial tumor tissue are visible D2-40of positive expression, but thymic epithelial tumor tissue of the expression was significantly higher than the normal thymus organization.2. Masaoka increased with the staging, thymic epithelial tumor tissue D2-40express positive and strength corresponding increase, that is D2-40of the expression with the TET invasive enhance and strengthen.3. The expression of D2-40and the thymus tumor patient age, the clinical stages, organization credits type and relative and gender, tumor size, and whether has nothing to do with myasthenia gravis.4. Cox regression analysis results showed that the more factors the clinical stage (P=0.002, relative risk7.055), pathology organization credits type (P=0.004, relative risk6.755) and D2-40expression (P=0.008, relative risk3.069) is the independent factors affecting the prognosis.5. The expressions of D2-40tested by immunohistochemistry could be used to explore and evaluate the latent of invasion and metastasis of TET, and provide some evidence for the further studying and treatment of TET.更多还原