【作者】 白薇琦；

【导师】 汤建国；

【作者基本信息】 浙江大学 ， 耳鼻咽喉， 2008， 硕士

【摘要】 背景和目的:鼻咽癌是一种常见的头颈部恶性肿瘤,世界卫生组织统计大约有80%的鼻咽癌发生于我国,鼻咽癌具有浸润和转移的特征。颈淋巴结转移为首发症状者占60%,98%的病理类型为低分化鳞状细胞癌。研究表明:环氧化酶—2（Cyclooxygenase-2）是催化前列腺素合成的限速酶,它和恶性肿瘤组织中前列腺素合成有关,在多种肿瘤的发生、发展、淋巴结转移中起重要作用。研究表明:EB病毒和鼻咽癌发生密切相关。其中,EB病毒DNA表达的潜伏膜蛋白1（Epstein-Barrvitus latent membrane protein-1,LMP1）具有多种生物学功能,是其主要的致癌因子。当前研究表明:COX-2、LMP1在鼻咽癌组织中存在高表达,但它们的相互关系如何,尚待进一步研究。本研究运用免疫组化技术检测了53例鼻咽癌组织中的COX-2、LMP1的表达情况,同时分析了两者之间的关系。材料和方法:53例鼻咽癌常规石蜡标本由浙江大学医学院附属邵逸夫医院病理科提供,为2000—2005年鼻咽癌活检标本,经HE染色确诊为鼻咽癌。其中男性24例,女性29例,年龄为18—81岁,平均年龄52岁。伴有淋巴结转移者38例,无淋巴结转移者15例。病理分型:角化型鳞状细胞癌4例,非角化性鳞状细胞癌27例,未分化癌22例。分期根据97UICC标准:T₁ 14例,T₂ 14例,T₃14例,T₄11例;N₀15例,N₁22例,N₂11例,N₃5例;Ⅰ期5例,Ⅱ期14例,Ⅲ期19例,Ⅳ期15例。8例鼻咽部慢性炎症常规石蜡切片标本也由浙江大学医学院附属邵逸夫医院病理科提供,HE染色确诊为鼻咽部慢性炎症,其中男性5例,女性3例,作为对照组。所有标本均经10%中性甲醛固定,石蜡包埋,5um连续切片,用SP免疫组化法检测COX-2、LMP1的表达,用SPSS12.0统计软件对实验数据进行统计。结果:1在鼻咽癌组织中,COX-2阳性表达率为71.70%（38/53）;LMP1阳性表达率为66.04%（35/53）。2 COX-2、LMP1的表达在鼻咽癌颈部淋巴结转移组中均明显高于无颈部淋巴结转移组（P＜0.05）,但在年龄、性别、病理类型、临床分期的分组中均无显著性差异（P＞0.05）。3在鼻咽癌组织中,LMP1和COX-2的表达存在正相关（r=0.797,P＜0.001）。结论:1 COX-2、LMP1在鼻咽癌组织中均有表达。2 COX-2、LMP1在鼻咽癌中的表达和鼻咽癌颈淋巴结转移存在显著相关性,但和年龄、性别、病理类型、临床分期无相关性。3 COX-2和LMP1在鼻咽癌组织中的表达呈正相关。LMP1可能通过多途径上调COX-2的表达,从而促进鼻咽癌颈部淋巴结转移。更多还原

【Abstract】 Background and Objective:Nasopharyngeal carcinoma（NPC）is the most common one of malignant tumor in head and neck.According to WHO statistics,80%of them happened in China.Nasopharyngeal carcinoma is characterized with infiltrating and metastasis.60%NPC patients have been founded with neck lymphatic metastasis at their first examination.98%NPC is poorly differentiated squamous cell carcinoma.Studies have demonstrated that cyclooxygenase-2（COX-2）is the rate-limiting enzyme prostaglandin, concerned with prostagland in synthetical and played an essential role in many tumors’ genesis,growth and lymph nodes metastasis.Studies have demonstrated the relationship between NPC and Epstein-Barr vitus（EBV） infection.Epstein-Barr vitus latent membrane protein-1（LMP1）is the primary carcinogen with multiple biological functions.Previous studies had demonstrated that NPC can express COX-2,LMP1 highly,but their association were not very clearly.In our experiment,the expressions of COX-2 and LMP1 were immunohistochemically studied in 53 NPC sections,we wanted to know the correlation between COX-2,LMP1 in NPC.Materials and Methods:53 nasopharynx biopsy specimens from patients with NPC who had been diagnosed definitely by pathology from Sir Run Run Shaw Hospital,Medical School of Zhejiang University from 2000 to 2005.The specimens included 24 male and 29 female patients（age ranged from 18 to 81 years old,mean age was 52 years old）.Neck lymph nodes metastasis in these patients was 38 cases,and none neck lymph nodes metastasis was 15 ones. Pathological classification:Keratinizing squamous cell carcinoma was 4 cases,nonkeratinizing squamous cell carcinoma 27,and undifferentiated carcinoma 22.Accordong to 1997 UICC classification,T₁ was 14 cases,T₂ 14 cases,T₃ 14 cases and T₄ 11 cases;N₀ was 15 cases,N₁ 22 cases,N₂ 11 cases and N₃ 5 cases;StageⅠwas 5cases,Ⅱ14 cases,Ⅲ19 cases andⅣ15 cases. 8 nasopharyngeal biopsy specimens were collected from patients with chronic nasopharyngeal who had been diagnosed definitely by HE stain in the same hospital（male 5 and female 3）,which were served as normal controls.All these tissue samples were fixed in 10%formaJdehyde solution after being obtained, then embedded in paraffin,5-micrometer thick sections were prepared for examining the expression of COX-2,LMP1 by streptavidin-peroxidase immunochemistry.All the datas were analyzed statistically with SPSS 12.0 software in computer.Result:1.In Nasopharyngeal carcinoma tissue,Positive expression rate of COX-2 was 71.70%（38/53）;Positive expression rate of LMP1 was 66.04%（35/53）。2.In Nasopharyngeal carcinoma tissue,there was significant relation of COX-2,LMP1 with N stage（P＜0.05）, none-significant ralation of COX-2,LMP1 with age,ender, tumor stage,clinical stage and pathological classification（P＞0.05）.3.In Nasopharyngeal carcinoma tissue,the expression of COX-2 showed a significant positive correlation with the expression of LMP1（r=0.797,P＜0.001）。Conclusion:1.The results suggested that COX-2,LMP1 were highly expressed in nasopharyngeal carcinoma cells.2.The expressions of COX-2、LMP1 were significantly associated with neck lymph nodes metastasis. none-significant ralation of COX-2,LMP1 with age,gender、tumor stage,clinical stage and pathological classification.3.The expression of LMP1 showed a significant positive correlation with the expression of COX-2,and it showed that LMP1 could enhance NPC metastasis by up-regulating the expression of COX-2.更多还原