子宫内膜癌组织中抑癌基因PTEN突变和表达的探讨

目的：研究抑癌基因PTEN在子宫内膜癌组织中的突变频率、分布和表达，探讨其在子宫内膜癌发病中的意义。方法：提取40例新鲜子宫内膜癌及癌周组织的基因组DNA，应用聚合酶键式反应—单链构象多态性分析(PCR—SSCP)方法，研究PTEN基因9个外显子的突变情况，并对突变样本进行测序分析。采用免疫组织化学法进行PTEN蛋白表达研究，并与组织学类型、临床分期、病理分级、淋巴结转移和雌孕激素受体状态的相关性进行分析。结果：40例子宫内膜癌中共检测到突变为18例，占45、0％。18例结果显示，8例为错义突变，10例分别为无意义突变、插入和缺失，形成截短蛋白。异常突变点中44、0％为外显子5，28.0％为外显子8，17．0％为外显子3，外显子1和6各有1例。免疫组化结果显示PTEN主要分布于细胞浆中：23／40例(57．5％)子宫内膜癌中PTEN表达完全缺失，10／40例(25．0％)表达部分缺失。PTEN在子宫内膜癌的表达与组织学类型和临床分期有关，与病理分级、肌层侵润及淋巴结转移无明显相关性。PTEN表达缺失率在雌孕激素受体阳性的癌组织中明显高于雌孕激素受体阴性的癌组织。结论：PTEN可能和子宫内膜癌的发生有关。

Study of Expression and Mutation of Tumor Suppressor PTEN in Endometrial Carcinoma

Objective:To study the mutation frequency,distribution and expression of tu-mor suppressor PTEN in endometrial carcinoma.Methods:Genomic DNA samples were extracted from40cases of fresh endometrial carcinoma tissues and their non-tumaor adjacent tissues.Poly-merase chain reaction-single strand conformation polymorphism(PCR-SSCP)methods was used to detected point mutation of nine exons of PTEN gene.Those showing abnormal DNAbands were se-quenced to veryfy the mutations.Protein of PTEN of the localization and quantification were study by Immunohistochemistry and respectly,in40cases endometrial carcinoma and10cases normal endometrium.Results:Among the40samples,18cases(45%)were found to have mutations.8cases were missense mutation,10cases can produce truncated protein by nonsense mutatons and/or frameshift mutations.Among mutation spots,8cases(44%)were found in exon5,5cases(28%)were found in exon8,3cases (17%)were found in exon3.1case was found in exon1and exon6re-spectively.PTEN was mainly distributed in cytoplasm.the absolute absence rate of PTEN was56%.The expression of PTEN was significantly associated with clinical stage and histological type.The absence rate of PTEN in endometrial carcinoma of ER/PR (+)was signifisantly higher than that of ER/PR(-).Conclusion:PTEN maybe was an early events in endometrial carcinogenesis.