【作者】 王谦；

【导师】 战忠利； 孙保存； 冯玉梅； 闫庆娜；

【作者基本信息】 天津医科大学 ， 病理学与生理学， 2008， 硕士

【摘要】 研究目的:首次探讨肠道病毒柯萨奇病毒B组(CVB)及柯萨奇病毒-腺病毒受体(CAR)在人非小细胞肺癌(NSCLC)中的表达情况,探寻三者之间的关系。试图寻找NSCLC的新病因,为Ad-p53用于NSCLC的临床治疗提供理论依据。方法:应用人体肺癌切除标本作回顾性分析,采用免疫组织化学染色方法检测120例手术切除的NSCLC组织的癌组织、癌旁和5例非癌肺组织标本中CAR及CVB的表达情况,分析CVB及CAR的表达与NSCLC的发生发展、临床病理特征及其它临床资料间的关系。结果:1 CAR的表达:CAR阳性染色为膜型。在非癌标本中,未发现CAR的阳性染色。鳞状细胞癌和腺癌中CAR的表达均上调,上调率分别为26.67%和31.46%,分析发现CAR的阳性表达量在两型肺癌的原发癌组织与癌旁组织中差别均有统计学意义(p＜0.05),提示CAR的阳性表达与两型肺癌有关,呈正相关(鳞状细胞癌r=0.29277,腺癌r=0.32579)。同时我们发现细支气管肺泡癌的阳性率86.38%。腺癌中如果剔除了细支气管肺泡癌成分,统计结果出现转变,即CAR的表达量在细支气管肺泡癌以外腺癌的原发癌组织与癌旁组织间差别尚不能认为有统计学意义(p＞0.05),CAR与细支气管肺泡癌以外的肺腺癌之间无关。CAR的表达与鳞状细胞癌的不同组织学分级无关。鳞状细胞癌和腺癌间CAR的表达量间差别、癌旁组织间差别亦不能认为有统计学意义(p＞0.05),我们的结果没有显示出CAR与NSCLC的某种亚型的关系更为密切。CAR在性别、年龄、肿瘤直径、淋巴结转移等方面的差别无统计学意义。2 CVB的表达:CVB阳性染色为胞浆型。在非癌标本中,未发现CVB的阳性染色。鳞状细胞癌和腺癌中CVB的表达均上调,上调率分别为30.00%和12.36%,分析发现CVB的阳性表达量在两型肺癌的原发癌组织与癌旁组织中差别均有统计学意义(p＜0.05),提示CVB的阳性表达与两型肺癌有关,呈正相关(鳞状细胞癌r=15.09317,腺癌r=5.28281)。这一点同于CAR的结果。但是,单独分析细支气管肺泡癌、除细支气管肺泡癌外的腺癌,发现CVB的表达量与两者均无关(p＞0.05)。CVB与鳞状细胞癌的不同组织学分级同样没有关系。另外与CAR结果一致的是,鳞状细胞癌和腺癌的癌旁组织间差别没有统计学意义(p＞0.05)。但是癌间CVB的表达量间差别有统计学意义(p＜0.05),鳞状细胞癌CVB阳性率比腺癌高16.98%,这显示出CVB与鳞状细胞癌的的关系更为密切。CVB在不同性别间的表达差别有统计学意义,男性组阳性率高于女性组15.10%,而CVB与年龄、肿瘤直径、淋巴结转移等因素无关。这说明男性更容易感染CVB。3 CAR和CVB的关系:在NSCLC中,CAR与CVB之间呈正相关(r=0.25128),其中在鳞状细胞癌、腺癌、除细支气管肺泡癌外的腺癌中,均呈现正相关(r分别为0.37741、0.29638、0.39590),但在细支气管肺泡癌的统计学分析中不能认为两者有关(p＞0.05),这需要大样本的细支气管肺泡癌加以证实。结论:1.非癌标本中未见CAR阳性染色。CAR的阳性表达与鳞状细胞癌呈正相关,与腺癌中的细支气管肺泡癌呈正相关,而与细支气管肺泡癌以外的肺腺癌之间无统计学相关性。与鳞状细胞癌的不同组织学分级无关。但是,我们的结果没有显示出CAR与NSCLC的某种亚型的关系更为密切。CAR与性别、年龄、肿瘤直径、淋巴结转移无关。部分解释并支持了Ad-p53的肺癌基因靶向治疗(例如对不能手术的鳞状细胞癌的局部注射治疗,气管内滴入Ad-p53治疗细支气管肺泡癌),并为肺癌的基因治疗提供了新的思路。CAR可能成为Ad-p53治疗的药敏指标。NSCLC中,CAR的表达量与CVB的感染之间呈正相关。2.非癌标本中未见CVB阳性染色,CVB的阳性表达与两型肺癌呈正相关。与鳞状细胞癌的不同组织学分级无关。与细支气管肺泡癌无关。CVB与鳞状细胞癌的的关系比腺癌更为密切。同时,男性更容易感染CVB。而与年龄、肿瘤直径、淋巴结转移等因素无关。我们在世界范围内首次探索并得出肠道病毒与肺癌有关,为寻找肺癌的病因开拓新的领域。这点还需从病毒的遗传物质等多角度检测。3.NSCLC中,CAR的表达量与CVB的感染之间呈正相关。更多还原

【Abstract】 Objective To discuss expression of CVB and CAR in NSCLC,and to study the relationship among CAR,CAR and the development of NSCLC.To discover new pathogeny of lung cancer and to optimize adenovirus vector-based gene therapy.Methods The expression of CAR and CAR in 120 cases of NSCLC,paraneoplastic epithelial tissue and 5 normal lung tissues was examined using immunohistochemistry.At the same time,the relationship among CAR and CAR expression and clinicopathologic characteristics was analyzed.Results1.Expression of CAR:All staining on the cell membrane,little in normal lung tissue. Compared with paraneoplastic tissue,CAR is up-regulated in tumor tissues.The possitive rate in squamous cell cancers was 26.67%,and in adenocinoma 31.46%.It shows that CAR and NSCLC are positive correlation(squamous cell cancers, r=0.29277,adenocinoma,r=0.32579).We noticed that 27 cases are positive in 32 bronchioalveolar adenocinoma,positive rate 86.38%.However,the difference in adenocinoma except bronchioalveolar adenocinomas,in stages of squamous cell cancer,in sex,age,tumor diameter、metastasis had no statistical significance had no statistical significance.The difference between tumor tissues of two types, paraneoplastic tissue,had no statistical significance.So our results did not show that CAR expression is needed for the formation of tumors by a subset of SNCLC.2.Expression of CVB:All intracellular staining,little in normal lung tissue. Compared with paraneoplastic tissue,CVB is up-regulated in tumor tissues.The possitive rate in squamous cell cancers was 30.00%,and in adenocinoma 12.36%.It shows that CVB and NSCLC are positive correlation(squamous cell cancers, r=15.09317,adenocinoma,r=5.28281).The difference in stages of squamous cell cancer,between tumor tissues,in age,tumor diameter、metastasis had no statistical significance,but had statistical significance in paraneoplastic epithelial tissue.It shows that CVB expression is correlate with squamous cell cancers closer than adenocinoma,and with 16.98%positive rate higher than in adenocinoma.15.10% positive rate in male higher than female shows that CVB infect easier in male.3 the correlation between CAR and CVB:CAR and CVB are positive correlation in NSCLC(r=0.25128),squamous cell cancers(r=0.37741),adenocinomas(r=0.29638), adenocinoma except bronchioalveolar adenocinomas(r=0.39590),but zero correlation in bronchioalveolar adenocinomas,maybe because of the little cases.Conclusion1 There is positive correlation between squamous cell cancers,bronchioalveolar adenocinomas and CAR,zero correlation between adenocinomas except bronchioalveolar adenocinomas and CAR,no relationship between stages of squamous cell cancer,sex,age,tumor diameter、metastasis and CAR.Our results did not show that CAR expression is needed for the formation a subset of SNCLC.This research provides a basis for planning a regimen of gene.2 There is positive correlation between NSCLC and CVB,no relationship between stages of squamous cell cancer,age,tumor diameter、metastasis and CAR.Statistical significance in paraneoplastic tissue shows that CVB expression is correlate with squamous cell cancers closer than adenocinoma,and CVB infect easier in male.Zero correlation between paraneoplastic epithelial tissue of two typies.At the first time,we discovered enteroviruses could cause lung cancer,and found a new pathogeny of lung cancer.And it needs further test.3 It is positive correlation between CAR and CVB in NSCLC.更多还原