摘要
目的:探讨p53突变在人脑胶质瘤发生发展中的作用及p53蛋白蓄积与突变的符合程度,并研究MDM2、p16、p53蛋白表达与胶质瘤临床病理特征的关系以及三者的相关性。方法:利用聚合酶链反应-单链构象多态性分析法(PCR-SSCP)及LSAB免疫组化法对已明确诊断的48例人脑胶质瘤进行p53基因突变以及MDM2、p16、p53蛋白表达的检测。结果:48例胶质瘤中20例p53蛋白呈阳性表达(41.7%)。PCR-SSCP检测发现17例(35.4%)呈现p53基因的单链构象多态性改变,均位于5～8外显子,突变例数依次为7(41.2%)、1(5.9%)、4(23.5%)、5(29.4%)。两种方法检测的符合率为89.6%(43/48)。MDM2、p53蛋白阳性率分别为22.9%、41.7%,p16表达缺失率为60.4%。在高级别(Ⅲ、Ⅳ级)的肿瘤中p53表达率及p16表达缺失率分别为63.2%、84.2%,均明显高于低级别(Ⅱ级)的肿瘤(分别为27.6%、44.8%)(P<0.05)。在不同分级的胶质瘤中,MDM2表达率及阳性程度没有显著差异。在p53阳性表达的病例中常伴有p16的表达缺失(57.6%),而且大多出现在Ⅲ、Ⅳ级肿瘤中(9/12)。p53突变、三种分子的表达均与患者的年龄、性别、肿瘤的大小及发病部位无相关性。结论:胶质瘤中p53基因的突变与胶质瘤的发生及恶性进展相关,p53蛋白蓄积与突变率较一致。MDM2基因异常参与胶质瘤的发生,是其形成的早期事件;p16、p53在胶质瘤中的异常表达与肿瘤的分化程度相关。
Objective： To investigate the effect of p53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, p53 and P16 protein in glioma formation and progression, as well as the correlations between them. Methods： The LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of the proteins MDM2, p53 and P16 and, the p53 gene mutation in 48 cases with human encephalic gliomas. Results： The positive expression rate of MDM2, p53 and the negative rate P16 protein was 22.9%, 41.7% and 60.4%, respectively. The expression of the p53 and the negative rate of P16 protein in the gliomas with high potential malignancy were significantly higher than that in those with low potential malignancy. Moreover, the co-expression of Mdm2 and p53 protein was confirmed in only 1 of the 48 cases. PCR-SSCP results showed that in 17 cases abnormal bands were detected in one of the 5-8 exons of p53 gene. The mutations were detected inl6 of the 20 cases with positive expression of p53 and the negative expression was found in another case. The concordance rate of immunohistochemistry and PCR-SSCP was 89.6%. In 7 cases （41.2%）, the mutations located in exon 5, 1 （5.9%）was in exon 6, 4 （23.5%） in exon 7 and 5 （29.4%） in exon 8, respectively, p53 gene mutation and the level of MDM2, p53 and P16 protein were not related to age, gender of patients, tumor location and size. Conclusion： The mutation of p53 and deletion of P16 may play an important role in the tumorigenesis of glioma and it is significantly associated with the differentiation of the tumor.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2006年第1期25-27,共3页
Chinese Journal of Clinical Oncology
基金
山东省教委计划项目基金资助(编号:J96K71)
关键词
神经胶质瘤
基因
突变
蛋白表达
Glioma Gene mutation Expression of the proteins
