宫颈鳞癌组织中p53和mdm2蛋白异常表达研究

Abnormal Expression of p53 and mdm2 Protein in Cervical Cancer Tissues

[目的]探讨p53和mdm2基因异常在宫颈癌发生发展中的作用以及两者间的相互关系。[方法]应用PCR鄄SSCP和免疫组化技术检测12例宫颈原位癌、45例宫颈癌和20例正常宫颈组织中p53基因突变以及p53和mdm2蛋白表达。[结果]①45例宫颈癌标本中测得exon5和exon7突变各1例,合计突变率为4.44%,宫颈原位癌和正常宫颈组织中均未检测到p53基因突变。②宫颈原位癌组织中p53和mdm2蛋白阳性率分别为25.00%和41.67%;宫颈癌组织中p53和mdm2蛋白阳性率分别为42.22%和53.33%。宫颈原位癌和宫颈癌组织中p53和mdm2蛋白的阳性率明显高于正常宫颈组织(P均<0.05)。③p53蛋白的表达与宫颈癌临床分期有显著相关性(P=0.042)。④22例p53蛋白阳性宫颈原位癌和宫颈癌组织中有17例同时检测到mdm2的表达,两者间有显著相关性(χ2=9.988,P=0.0016)。[结论]宫颈癌组织中p53基因突变率较低,提示p53基因突变并非宫颈癌组织中p53蛋白异常表达的主要原因。p53蛋白异常表达的宫颈原位癌和宫颈癌组织中多伴有mdm2表达,推测mdm2蛋白可能通过干扰p53的功能参与宫颈癌的发生。

To explore the abnormality of p53 and mdm2 gene and their relationship in genesis of cervical cancer.p53 gene mutation in exon 5～8 was tested by PCR-SSCP,and the expression of p53 and mdm2 protein was examined by immunohistochemistry in 12 cases with carcinoma in situ(CINⅢ),45 cases with cervical cancer and 20 cases with normal cervical tissues. ① Each one case with exon 5 and exon 7 p53 mutation was found in one each respectively in 45 cases of cervical cancer.No p53 gene mutation was found in all of CINⅢ and normal cervical tissues.②The positive rate of p53 and mdm2 were 25%,41.67% in CINⅢ respectively,42.22%,53.33% in cervical cancer respectively.Both posilive rates were significantly higher than those in normal cervical tissues(P<0.005). ③There was significant correlation between clinical stage and abnormal expression of p53 protein(P=0.042).④ Seventeen caes with co-expression of mdm2 and p53 protein were found in 22 cases of CINⅢ and cervical carcinomas with positive p53 expression.The mdm2 protein expression was associated with p53 protein expression significantly(χ2=9.988,P=0.0016).[Conclusion]Low frequency of p53 gene mutation in cervical cancer tissues suggests that p53 protein abnormal accumulation may not result from p53 gene mutation.The expression of mdm2 is closely related with abnormal expression of p53 protein.The mdm2 protein may play an important role in the pathogenesis of cervical cancer through interacting with p53 protein.