【作者】 袁春艳；

【导师】 吴翠环；

【作者基本信息】 华中科技大学 ， 病理与病理生理学， 2006， 硕士

【摘要】 【目的】1.探讨HPV感染在NSCLC发生中的病因学意义;2.研究NSCLC中HPV感染与p53及Survivin蛋白表达及细胞凋亡之间的关系,初步探讨HPV感染与NSCLC发生的相关分子机制;3.分析HPV感染、p53及Survivin蛋白表达与临床病理特征的关系。【方法】采用PCR方法选用HPV16、18型特异性引物分别检测76例NSCLC及13例肺良性病变组织中是否存在HPV DNA的表达;免疫组化SP法检测p53和Survivin蛋白在NSCLC和肺良性病变组织中的表达水平; TUNEL法检测NSCLC组织中凋亡指数(AI)。【结果】1. PCR检测HPV DNA的结果HPV DNA检出率肺癌组为40.8%(31/76),肺良性病变组为7.7%(1/13),两者有显著性差异(P <0.05)。2. NSCLC中HPV感染与p53、Survivin蛋白表达及细胞凋亡之间的关系NSCLC中p53和Survivin蛋白表达总阳性率分别为63.2%(48/76)和42.1% (32/76),肺良性病变组均未见表达。NSCLC中HPV阳性组和阴性组p53蛋白表达阳性率为80.6%(25/31)和51.1%(23/45)(P <0.05)。p53蛋白表达阳性组和阴性组中,Survivin蛋白表达阳性率为54.2%(26/48)和21.4%(6/28)(P <0.05)。HPV DNA阳性且p53蛋白阳性组和HPV DNA阴性而p53蛋白阳性组中,Survivin蛋白阳性表达率分别为64.0%(16/25)和34.8%(8/23)(P <0.05)。NSCLC中HPV DNA阳性组AI值较阴性组明显降低,分别为(1.09±0.96)%和(5.87±2.64)%(P <0.05); p53蛋白表达阳性组AI较阴性组显著降低,分别为(1.12±0.38)%和(3.26±0.87)%(P <0.05); Survivin蛋白表达阳性组AI较阴性组显著降低,分别为(0.82±0.48)%和(3.13±0.57)%(P <0.05)。3. NSCLC中HPV感染、p53和Survivin蛋白表达与临床病理特征的关系NSCLC中HPV感染和分化程度及吸烟相关,而与年龄、性别、组织学类型、淋巴结转移无关。高、中、低分化肺癌HPV DNA检出率分别为60.0%(9/15)、53.3%(16/30)、19.4%(6/31),高、中分化肺癌HPV DNA检出率明显高于低分化肺癌(P <0.05)。吸烟患者HPV感染率52.0%(26/50)明显高于不吸烟患者19.2% (5/26)(P <0.05)。p53蛋白阳性表达与患者年龄、性别、吸烟史及NSCLC分化程度、淋巴结转移等无关,而与组织学类型相关,肺鳞癌和腺癌中p53蛋白阳性表达率分别为85.4%(35/41)和37.1%(13/35),两者有显著性差异(P <0.05)。Survivin蛋白阳性表达与患者年龄、性别、吸烟史及NSCLC分化程度、组织学类型、淋巴结转移等均无关(P >0.05)。【结论】1. HPV感染与NSCLC的发生密切相关,且与NSCLC分化程度及吸烟有关,提示HPV感染可能是导致NSCLC发生的重要病因学因素之一,吸烟很可能协同HPV感染共同参与肺癌的发生;2.肺癌组p53蛋白表达与HPV感染相关,HPV可能诱导p53突变,突变的p53丧失对凋亡抑制基因Survivin的负调控机制,从而Survivin蛋白表达增加,抑制肿瘤细胞凋亡,促进肺癌的发生。更多还原

【Abstract】 【Objection】1. To investigate the etiological role of HPV on the carcinogenesis of NSCLC;2. To study the relationship between HPV infection and the expression of p53、Survivin protein and cell apoptosis, and to elucidate the possible molecular mechanisms that HPV infection induced carcinogenesis of NSCLC;3. To study the relationship between HPV infection、the expression of p53 and Survivin protein and clinical pathological characteristics.【Methods】76 cases of NSCLC and 13 cases of lung benign diseases were respectively examined by PCR to detect the HPV positive rate by HPV16、18 type-specific primers. The protein expression levels of p53 and Survivin in NSCLC and lung benign tissues were detected by SP immunohistochemistry. TUNEL was applied to detect apoptosis index (AI) in NSCLC.【Results】1. the result of HPV DNA detected by PCR Detection rate of HPV DNA in lung cancer group was 40.8% (31/76)and that in benign diseases group was 7.7%(1/13). There was a significant difference between the two groups ( P <0.05 ).2. the relationship between HPV infection and the expression of p53 and Survivin protein and the apoptosis of cellsExpression rate of p53 and Survivin protein was 63.2% (48/76) and 42.1% (32/76) in NSCLC. There was no expression in benign tissues. Expression rate of p53 protein was 80.6%(25/31) in HPV DNA positive group in NSCLC. It was significantly higher than that in HPV DNA negative group51.1%(23/45)(P <0.05).The positive rate of Survivin expression in p53 positive group 54.2%(26/48) was significant higher than in negative one 23.1%(6/28).The positive rate of Survivin expression in HPV DNA positive with p53 protein positive and HPV DNA negative but p53 protein positive group was 64.0%(16/25) and 34.8%(8/23) ( P <0.05 ).There was statistic significance of AI between HPV DNA positive(1.09±0.96)% and negative(5.87±2.64)% group in NSCLC(P <0.05). There was statistic significance of AI between p53 positive(1.12±0.38)% and negative(3.26±0.87)% group in NSCLC(P <0.05). There was statistic significance of AI between Survivin positive(0.82±0.48)% and negative(3.13±0.57)% group in NSCLC(P <0.05).4. the relationship between HPV infection、the expression of p53 and Survivin protein and clinical pathological characteristics.No correlation was found between HPV infection rate and age、sex、lymph node metastasis and histological type of patient. But there was a significant correlation between HPV infection rate and degree of differentiation、history of smoking(P <0.05). The rate of HPV DNA in highly differentiated NSCLC was 60.0% (9/15) and that in moderately differentiated NSCLC was 53.3% (16/30). HPV infection rate in smoking lung cancer patients 52.0%(26/50) was significantly higher than that in non-smokers 19.2%(5/26) ( P <0.05 ).No correlation was found between the expression of p53 protein and age、sex、history of smoking、lymph node metastasis and degree of differentiation, but there was significant difference between the expression of p53 protein and histological type of NSCLC. The expression rate of p53 protein in lung squamous cell carcinoma 85.4%(35/41) was significantly higher than that in adenocarcinoma 37.1%(13/35) ( P <0.05 ). No correlation was found between the expression of Survivin protein and age、sex、history of smoking、lymph node metastasis degree of differentiation and histological type of NSCLC(P >0.05).【Conclusion】1. There was relationship between HPV infection and NSCLC, and HPV infection was related to degree of carcinoma differentiation and smoking. It suggested that HPV infection was one of important etiological factors in carcinogenesis of NSCLC. Smoking cooperated with HPV infection in the occurrence of NSCLC.2. There was relationship between the expression of p53 protein in lung cancer group and HPV infection. HPV might induce p53 mutation, Mutative p53 promoted the expression rate of Survivin, and apoptosis of cells was inhibited. It accelerated the occurrence of NSLCL.更多还原