维、汉族妇女宫颈病变进程与雌激素受体1(ESR1)蛋白表达缺失的关系

Association of Cervical Disease Pathogenesis of Uighur and Han Women with the Loss of Estrogen Receptor 1 (ESR1) Protein Expression

以往的报道显示宫颈癌组织内的雌激素受体1(Estrogen Receptor 1,ESR1)基因启动子发生高度甲基化,并提示其基因表达水平可能下降或基因休眠。本研究从蛋白质水平观察ESR1表达缺失与宫颈病变进程的关系及其维、汉妇女族群差异。收集维吾尔族和汉族妇女宫颈炎、宫颈内上皮瘤样病变(Cervical Intraepithelial Neoplasia,CIN)I/II/III和宫颈鳞癌患者的福尔马林浸泡与石蜡包埋宫颈组织标本共180例,采用免疫组织化学方法鉴定ESR1蛋白表达水平。结果显示,ESR1蛋白在宫颈上皮和间质细胞均有表达,但是随着CIN和宫颈鳞癌的发病进程,其在上皮细胞内的表达逐渐发生缺失;ESR1蛋白表达缺失率在宫颈炎和CIN I组较低(22%),CIN II/III组明显升高(64%),宫颈鳞癌达到最高(76%),各组之间差异显著(P<0.01),但是在个体年龄之间无统计学差异(P>0.05)。维、汉妇女族群ESR1表达缺失率的变化趋势有共性,其族群差异也无统计学意义(P>0.05)。由此表明,ESR1表达缺失可能是宫颈鳞癌的早期预警指标,这为揭示该基因高度甲基化相关的表观遗传学机制提供了重要依据。

Previous reports show a hypermethylation of estrogen receptor 1 （ESR1） gene promoter in cervical carcinoma and it was suggested that this may lead to down regulation of gene expression or gene silencing. This paper studies the association of ESR1 loss at the protein level with the cervical disease pathogenesis, and its relation to ethnic differences between Uighur and Han women. A total of 180 cases of formalin fixed and paraffin-embedded cervical tissue specimens were collected from Uighur and Han women with cervicitis, cervical intraepithelial neoplasia （CIN） Ⅰ/Ⅱ/Ⅲ and cervical squamous cell carcinoma, and the ESR1 protein expression was detected by immunohistochemistry. Experimental results show that ESR1 protein is ubiquitously expressed in both epithelial and stroma cells of the uterine cervix, but gradually lost in epithelial cells with the development of CIN and cervical squamous cell carcinoma. The loss rate of ESR1 protein expression is relatively low in the group of cervicitis and CIN Ⅰ, is markedly increased in the group of CIN Ⅱ/Ⅲ （64%）, to reach the highest level in cervical carcinoma （76%）, and the difference is significant among groups （P〈0.01）, but no statistical difference inages of the individuals （P〉0.05）; the alteration trend of the loss rate of ESR1 is common to women from both Uighur and Han ethnic groups, and the difference between two ethnic groups is also not statistically significant （P〉0.05）. These results indicate that the loss of ESR1 expression may be an early prediction marker of cervical squamous cell carcinoma, which may serve as an important evidence for revealing epigenetic mechanisms related to the hypermethylation of this gene.