原发性子宫内膜癌与p16基因突变及蛋白表达关系的研究

目的研究p16蛋白表达与原发性子宫内膜癌发生发展的关系和p16基因缺失突变及点突变在原发性子宫内膜癌发生发展中的地位.方法利用免疫组织化学方法、聚合酶链反应和聚合酶链反应-单链构象多态性分析技术,分别检测正常子宫内膜组织、子宫内膜癌前病变组织及原发性子宫内膜癌组织,观察p16蛋白和p16基因缺失突变及点突变.结果1)p16蛋白阳性表达率在正常子宫内膜组织和子宫内膜癌前病变组织中表达率分别为92.78%和90.00%,两者相比无差异性;在原发性子宫内膜癌组织中为66.67%,明显低于正常子宫组织及癌前病变组织;2)在42例原发性性子宫内膜癌组织中有14例发生p16基因缺失突变,4例发生了p16基因点突变,突变率为分别为33.33%和9.6%,正常子宫颈组织和子宫内膜癌前病变组织未发现p16基因缺失突变和点突变.结论1)在原发性子宫内膜癌发生发展过程中,p16蛋白的表达在高分化癌明显低于低分化癌,表明p16蛋白缺乏与子宫颈细胞增殖失控及分化不良紧密相关.2)原发性子宫内膜癌存在p16基因点突变,以低分化癌多见,但不是较频繁的事件;原发性子宫内膜癌存在p16基因缺失突变,以低分化癌多见,是较频繁的事件.3)p16蛋白表达与p16基因突变的相关性未被发现.

Relationship Research of Primary Endometrium Cancer with p16 Gene Mutation and Protein Expression

Objective To investigate the relationship between expression of p16 protein and primary endometrium cancer and to evaluate the role of p16 gene delection mutation and point mutation in primary endometrium carcinoma.Methods Streptavidin-peroxidase conjugated method was performed for detecting the expression of p16 proteins in cases of normal endometrium,cases of the anterior lesion of endometrium cancer and cases of primary endometrium carcinoma,and polymerase chain reaction and polymerase chain reaction single-strand conformation polymorphism analysis for p16 gene deletion mutation and point mutation.Results 1)The expression rate of p16 protein in normal endometrium and the precancerous lesion of endometrium is 92.78% and 90.00%,no difference is found between them,and the rate is 66.67% in primary endometrium cancer,much lower than that in normal endometrium and the precancerous lesion of endometrium.2)There are 14 cases of loss mutation and 4 cases of point mutation among 42 cases of primary endometrium carcinoma,and the rate of mutation is 33.33% and 9.6%.There is not loss mutation and point mutation found in normal endometrium and the precancerous lesion of endometrium cancer.Conclusion 1)In the course of generation and development of primary endometrium cancer,the expression level of p16 protein in highly-differentiated cancer is much higher than that in poorly-differentiated cancer,which displays that there is a close correlation between the absence of p16 protein and endometrium cell proliferation miss control and dysplasia.2)The point mutation of p16 gene is found in primary endometrium cancer,mainly in the poorly-differentiated cancer,but it is a less frequency.p16 gene deletion mutation is found in primary endometrium cancer,mainly in poorly differentiated cancer,and it is a frequency and late phase event.3)It is not found correlation between expression of p16 protein and p16 gene mutation.