组织因子途径抑制物-2在卵巢浆液性囊腺癌组织中的表达及甲基化修饰

The protein expression and DNA methylation modification of tissue factor pathway inhibitor-2 in ovarian serous cancer tissue

目的探讨组织因子途径抑制物-2（tissue factor pathway inhibitor,TFPI-2）基因在卵巢浆液性囊腺癌与卵巢浆液性囊腺瘤组织中表达差异情况,以及与其启动子区DNA甲基化的关系。方法应用免疫组化技术分析46例卵巢浆液性囊腺癌组织和66例卵巢浆液性囊腺瘤组织中TFPI-2基因蛋白表达水平;用甲基化特异性PCR法（MS-PCR）检测TFPI-2基因启动子区DNA甲基化水平。结果卵巢浆液性囊腺瘤组织中TFPI-2蛋白表达阳性率为62.12%（41/66）,高于卵巢浆液性囊腺癌组织39.13%（18/46）,两组间差异有统计学意义（χ~2=5.748,P=0.017）;卵巢浆液性囊腺瘤组织与卵巢浆液性囊腺癌组织中TFPI-2基因甲基化阳性率分别为72.73%、78.26%,两组间差异无统计学意义（χ~2=0.443,P=0.506）,而低分化卵巢浆液性囊腺癌组织TFPI-2基因甲基化比率50.00%显著低于中、高分化组88.24%,两组差异有统计学意义（χ~2=5.540,P=0.019）。结论 TFPI-2蛋白表达与卵巢肿瘤的病理进展呈负相关,其启动子区DNA甲基化水平与卵巢癌细胞分化程度有关。

Objective To observe the difference of TFPI-2gene expression in tissues of ovarian serous cancer and ovarian serous cystadenoma,and explore the relationship between gene expression and DNA methylation in promoter region of TFPI-2gene. Methods Immunohistochemistry（IHC）and MS-PCR were used to determine the expression of TFPI-2and DNA methylation in promoter region of TFPI-2gene in tissue samples from 46 cases of ovarian serous cancer and 66 cases of ovarian serous cystadenoma. Results The positive rate of protein expression of TFPI-2in ovarian serous cystadenoma tissues was significantly higher than that in ovarian serous cancer（62.12%vs 39.13%）,the difference was significant（χ~2=5.748,P=0.017）.However,the positive rate of the DNA methylation of TFPI-2gene in ovarian serous cystadenoma and ovarian serous cancer tissues was not statistically significant（72.73%vs 78.26%）（χ~2=0.443,P=0.506）.While,the rate of methylation of TFPI-2gene in poorly differentiated ovarian serous cancer tissues was significantly lower than that in medium or high differentiated ones（50.00%vs 88.24%）（χ~2=5.540,P=0.019）. Conclusions TFPI-2expression is negatively correlated with the pathological progress of ovarian tumor,and the DNA methylation in promoter region is related to the differentiation of ovarian cancer cells.