【作者】 刘铁利；

【导师】 孙雷；

【作者基本信息】 大连医科大学 ， 病理学与病理生理学， 2009， 硕士

【摘要】 目的:肺癌成为导致死亡的主要原因之一,近20年来,我国肺癌导致的死亡超过癌症总死因的20%,而且发病率及死亡率增长最为迅速,是我国的第一大癌症。目前全球发病率仍以每年0.5%的速度增长,世界卫生组织报告肺癌将是21世纪危害人类最严重的常见病。非小细胞肺癌(NSCLC)约占肺癌总数的80%,流行病学资料显示,肺癌占我国城市人口死亡的第一位,主要原因是大多数肺癌患者发现时已经是晚期,大约90%患者死于肿瘤浸润、转移。肺癌的发生发展是多因素、多阶段、多基因改变共同作用的结果,涉及多种癌基因的激活和抑癌基因的失活。近年来研究表明,恶性肿瘤细胞凋亡机制受损与肿瘤发生、发展与消退有密切关系。聚集素Clusterin是近年新发现的凋亡抑制蛋白,它广泛表达于各种组织及体液中,并参与多种生理及病理过程:包括免疫调节、细胞粘附、脂质转运、组织重构、膜循环及细胞凋亡、细胞周期调节等,对肿瘤发生发展具有重要作用。细胞凋亡是一个复杂的过程,天冬氨酸特异性半胱氨酸蛋白酶(Caspases)家族的激活是细胞凋亡发生机制中最关键的环节之一,天冬氨酸特异性半胱氨酸蛋白酶3(aspartate- specificcysteine proteases 3, Caspase-3)是该家族最重要效应成员,在凋亡执行阶段负责对全部或部分关键性蛋白酶的水解裂解,Caspase-3被激活后,细胞将不可逆转的走向凋亡。本研究应用免疫组织化学S-P方法联合检测Clusterin与Caspase-3在NSCLC中的表达,并以正常肺组织作对照,结合临床病理资料,探讨Clusterin与Caspase-3在非小细胞肺癌中表达的特点及意义。材料和方法:本实验收集经病理证实的非小细胞肺癌标本52例,其中男性37例,女性15例;鳞癌21例,腺癌31例;高分化11例,中分化22例,低分化19例;Ⅰ-Ⅱ期28例,Ⅲ期24例;有淋巴结转移27例,无淋巴结转移25例。20例正常肺组织作对照。标本经10%甲醛固定,石蜡包埋。Clusterin与Caspase-3检测采用免疫组织化学S-P法,实验数据采用SPSS13.0统计软件包进行统计分析。结果:1.Clusterin在非小细胞肺癌中的阳性表达率为78.85%,明显高于正常肺组织的阳性表达率10%(P<0.05);Clusterin的阳性表达与肿瘤的分化程度、TNM分期及淋巴结转移有关(P<0.05);Clusterin的阳性表达与非小细胞肺癌的病理类型无关(P>0.05)。2.Caspase-3在正常肺组织中的阳性表达率为80%,明显高于在非小细胞肺癌中的阳性表达率44.23%;Caspase-3的阳性表达与肿瘤的分化程度、淋巴结转移有关(P<0.05);Caspase-3的阳性表达与非小细胞肺癌的病理类型、TNM分期无关(P>0.05)。结论:1.Clusterin在非小细胞肺癌中呈高表达,并与癌组织的病理分化程度、TNM分期及淋巴结转移相关,提示Clusterin可能与非小细胞肺癌的发生、发展及恶性潜能有关。2.Caspase-3在非小细胞肺癌中表达降低,并与癌组织的病理分化程度、淋巴结转移密切相关,提示Caspase-3的表达缺失可能与非小细胞肺癌的发生、发展及恶性潜能有关。更多还原

【Abstract】 Objective: Lung cancer is responsible for the cancer deaths in both men and women throughout the world, and is the number-one cause of cancer deaths in China due to incidence and mortality (more than 20%) increasing dramatically over the last 2 decades. And it is estimated that 0.5% new cases will be diagnosed per year and lung cancer remains among the most common types of cancers worldwide in the 21st century. Non-small cell lung carcinoma (NSCLC) is the most common lung cancer, accounting for about 80% of all lung cancers. Epidemiology data shows lung cancer is the most common cause of cancer death in China, since being diagnosed, most of the cases are in advanced stages and 90% died from carcinoma infiltration and metastasis. The occurrence mechanism of lung cancer depends on alteration of multi-factors, multi-stages and multi-genes, involving many kinds of oncogene activation and anti-oncogene inactivation. The incidence, development and subside of lung cancer is strongly correlated with apoptosis damage of malignant carcinomas, reported by recently research. Clusterin is a new apoptosis inhibitor protein and an important factor causing carcinoma, expressing in all kind of tissue and body fluid, attending physiological and pathological progresses, including immune regulation, cell adherion, lipid transportation, tissue remodeling, membrane recycling and cell-cell interactions and adjustment of apoptosis and cell cycle. The activation of aspartate-specific cysteine proteases (Caspases) is the most important stage in the complicated apoptosis process, and Caspase-3 is the most important effective number, which responsible for hydrolyses and splitting of all/part key proleases during apoptosis. Once Caspase-3 is activated, the cell apoptosis goes to inreversible stage. This research is to evaluate the expression and clinical significance of Clusterin and Caspase-3, with detecting their expression in NSCLC compared with benign tissue by immunohistochemistry S-P method combining with clinical pathology.Materials and Methods: 52 surgically resected non-small cell lung carcinoma tissues were collected. Among them male 37, female 15;21 cases were squamous cancer, 31 cases were adenocarcinoma;There were well-differentiated 11, moderate 22, poorly-differentiated 19; and there were 28 cases in stage I-II ,and 24 cases in stageⅢ;and there were lymph nodes metastasis in 27, and no lymph nodes metastasis in 25; 20 benign lung tissues specimens were collected as control groups. All the tissues were fixed in 10% neutral formalin and embedded in paraffin. S-P immmno- histochemical method was performed to detect the expressions of Clusterin and Caspase-3. The data were analyzed by software SPSS 13.0.Results:1.The positive rate of Clusterin in NSCLC (78.85%) ,was significantly higher than that of Clusterin in benign tissues (10%)( P<0.05); There was significant difference of Clusterin expression between pathological grade, and TNM staging, and lymph node metastasis P<0.05; The expression of Clusterin has no significant difference with histological type (P >0.05).2.The positive rate of Caspase-3 in benign tissues (80%) ,was significantly higher than that of Caspase-3 in NSCLC (44.23%)( P<0.05); There was significant difference of Caspase-3 expression between pathological grade,and lymph node metastasis P<0.05; The expression of Caspase-3 has no significant difference with histological type, TNM staging (P >0.05).Conclusions:1.Overexpression of Clusterin was related with pathologied grades and TNM staging and lymph nodes metastasis in NSCLC. Clusterin may participate in the occurrence and development of NSCLC.2.The low expression of Caspase-3 in NSCLC was closely related with pathological grades and lymph node metastasis, and may participate in the occurrence and development of NSCLC.更多还原