喉鳞状细胞癌患者p53表达、突变及72位氨基酸多态性及其与HPV感染的关系  

Analyzation of TP53 expression, mutation, codon 72 polymorphism and the relationship with humanpapillomavirus infection of the Chinese Laryngeal squamous cell carcinoma patients

作　　者：魏炜[1] 肖康[2] 张宝云[2] 张乃嵩[1] 董小平[2] 石琦[2] 

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所头颈外科,恶性肿瘤发病机制及转化研究教育部重点实验室,100142 [2]中国疾病预防控制中心病毒病预防控制所传染病预防控制国家重点实验室

出　　处：《中华实验和临床病毒学杂志》2014年第2期135-138,共4页Chinese Journal of Experimental and Clinical Virology

基　　金：传染病预防控制国家重点实验室基金（2012SKLIDl02,2011SKLID211）;国家自然科学基金（81301429）;传染病预防控制国家重点实验室自主研究开放课题（2012SKLID302）

摘　　要：目的了解喉鳞状细胞癌患者p53表达、突变，72位氨基酸多态性与HPV感染的关系方法在该研究中收集了64份石蜡包埋的病理标本，用PCR的方法对p53基因进行扩增、测序和分析，用免疫组织化学的方法对p53蛋白进行检测，并且应用功能分析软件对突变蛋白进行功能分析。应用统计学软件分析p53的突变与72位密码子多态性以及其他因素的关系。结果在64例临床诊断的喉癌病例中，通过PCR及测序的方法发现在p53基因高变区内22例病例具有30个突变。利用免疫组织化学的方法发现20例病例出现阳性改变。通过功能预测发现，大部分突变后的p53蛋白均丧失了其功能，只有4个突变点没有影响功能。72位密码子为精氨酸组的病例年龄（60岁）比脯氨酸组的病例年龄（55岁）偏大，但无统计学差异。结论喉癌病例中p53基因的突变是常见的现象，是喉癌发生的原因之一。Objective To analyze the expression, mutation and codon 72 polymorphism in the Chinese laryngeal squamous cell carcinoma patients and the relationship with HPV infection. Methods The paraffin-embedded tissue blocks from 64 pathological-diagnosed laryngeal squamous cell carcinoma patients were included in this study. PCR and direct sequencing were used to screen the mutations in TP53 gene and immunohistochemistry was used to evaluate the expressing profiles of p53 proteins. Functional analysis software online were used to analyze the function changes of mutated p53 proteins. The relationship between TP53 mutation and phenotypes of SNP72 with other features of the patients was analyzed by Chi- square and Fisher＇ s exact test. Results Out of 64 laryngeal squamous cell carcinoma patients, sequencing confirmed 30 TP53 mutations in 22 cases （73.3%） and p53 immunohistochemistry （IHC） confirmed 20 （31.3%） positive staining. Online software analysis showed that most of the mutated p53 proteins lost their normal function. Analyses of SNP72 polymorphism revealed that the patients with Arg phenotype had significantly older onset ages than those with Pro phenotype but without statistic difference. Conclusion TP53 mutations are frequently observed in Chinese patients with laryngeal squamous cell carcinoma and this is one of the pathogenesis for laryngeal squamous cell carcinoma.

关 键 词：癌 鳞状细胞 蛋白质P53 多态现象 乳头状瘤病毒 人 

分 类 号：R739.65[医药卫生—肿瘤]