宫颈癌与正常宫颈组织中ER、GPR30表达情况的相关研究

发布时间：2018-05-29 11:54

  本文选题：宫颈癌 + 雌激素受体　； 参考：《北京协和医学院》2015年博士论文

【摘要】：宫颈癌是女性常见的恶性肿瘤,在生殖系统肿瘤中占首位。我国女性中,宫颈癌的发病率仅次于乳腺癌而在恶性肿瘤中居于第二位,严重影响女性健康。宫颈癌的发生于人乳头瘤病毒(HPV)的感染有明确的相关性。正常宫颈从HPV感染到发生癌变需要经过漫长的过程,因此,期间应该还受到其他因素的影响。雌激素是人体内重要的性激素,与女性正常生理功能的发育和维持中都起到重要作用,同时也是导致多种女性恶性肿瘤发生的危险因素。关于雌激素对乳腺癌、子宫内膜癌影响的研究已有很多。但其与宫颈癌的关系,许多研究还没有明确定论。但人们已经认识到,雌激素对宫颈癌的发生和预后都具有一定的影响。雌激素在细胞内起作用的方式主要是与雌激素受体结合。研究较多的是雌激素受体(ER),近年来,雌激素的另一种受体G蛋白偶联受体30(GPR30)也逐渐受到重视。GPR30是一种主要定位于细胞器的跨膜蛋白,它与雌激素结合之后主要通过非基因组途径,激活下游EGF/MAPK等信号转导通路而发挥作用。GPR30可能在肿瘤的发生发展中发挥作用,但关于其在宫颈癌组织中的表达与功能,尚无明确报道。本文中,我们收集了宫颈癌患者组织标本；同时以因良性病变行子宫切除术的正常宫颈组织作为对照,各计37例。我们采用对病理切片进行免疫组化染色的方法,考察正常宫颈组织和宫颈癌组织中雌激素的两种受体ER、GPR30的表达水平。在37例正常宫颈组织中,ER的阳性率100%,GPR30阳性率16.2%； 37例宫颈癌组织中,ER的阳性率27%,GPR30阳性率51.3%。宫颈癌组织中,ER的表达明显低于对照组,而GPR30的表达明显升高。我们进一步分析GPR30表达与宫颈癌患者临床指标的关系。GPR30(+)在绝经患者中的比例高于未绝经患者,其在中至高分化的宫颈癌中比例较高。而在临床分期较高的宫颈癌患者中,GPR30的阳性稍高。GPR30阳性与宫颈癌患者的病理类型未见明显相关,其与淋巴结转移的相关性较ER明显。因此我们可以看出,GPR30在宫颈癌组织中的表达明显高于对照组,这提示了GPR30的异常活化促进宫颈癌发生的可能性。结合临床,我们认为GPR30有可能作为治疗宫颈癌的潜在靶点。同时,绝经后宫颈癌患者GPR30的相对高表达,提示对于这部分患者的绝经后雌激素补充疗法应予慎重考虑。本研究的主要问题是病例数相对较少,因为对于许多现象,仅能提示某种倾向而不足以得出较确实的结论。在今后的研究中,一方面应扩大样本量,另一方面也应补充宫颈上皮内瘤样病变(CIN)的标本。同时可以通过长期随诊,考察GPR30阳性的宫颈癌患者的预后情况,为临床提供更多的指导意义。
[Abstract]:Cervical cancer is the most common malignant tumor in women and is the first in the reproductive system tumor. Among the women of our country, the incidence of cervical cancer is second in the malignant tumor after breast cancer, which seriously affects the health of women. The occurrence of cervical cancer has a clear correlation with the infection of human papillomavirus (HPV). The normal cervix from the HPV infection to the occurrence of the infection. Cancer needs a long process, and therefore, it should be influenced by other factors. Estrogen is an important sex hormone in the body, plays an important role in the development and maintenance of normal physiological functions of women, and is also a risk factor for many female malignant tumors. There are many studies on the impact of cancer. However, many studies have not been made clear about the relationship with cervical cancer. However, it has been recognized that estrogen has a certain effect on the occurrence and prognosis of cervical cancer. The way estrogen acts in cells is mainly associated with estrogen receptor. More studies are estrogen receptor (ER) in recent years. The other receptor, G protein coupled receptor 30 (GPR30), is also gradually valued as a transmembrane protein that is mainly located in organelles. After binding to estrogen, it activates signal transduction pathways, such as downstream EGF/MAPK, mainly through non genomic pathways, and.GPR30 may play a role in the development of tumor. However, there is no clear report on its expression and function in cervical cancer. In this article, we collected tissue specimens of cervical cancer patients; at the same time, we used the normal cervical tissue of hysterectomy for benign lesions as control, each of 37 cases. We used immunohistochemical staining method to investigate the normal cervix of the cervix. The expression level of two kinds of estrogen receptor ER and GPR30 in tissue and cervical cancer tissues. In 37 normal cervical tissues, the positive rate of ER was 100%, and the positive rate of GPR30 was 16.2%. In 37 cases of cervical cancer, the positive rate of ER was 27% and the positive rate of GPR30 was 51.3%. in the cervical cancer tissues, the expression of ER was significantly lower than that of the control group, and the expression of GPR30 increased obviously. The relationship between GPR30 expression and the clinical index of cervical cancer patients.GPR30 (+) in menopause patients was higher than that of the non menopause patients, and the proportion was higher in the middle to high differentiation cervical cancer. In the patients with higher clinical stage, the GPR30 positive slightly higher.GPR30 positive than the pathological type of the cervical cancer patients had no obvious phase. The correlation with lymph node metastasis is more obvious than ER. Therefore, we can see that the expression of GPR30 in cervical cancer tissues is significantly higher than that of the control group, which suggests the possibility of abnormal activation of GPR30 to promote cervical cancer. We think that GPR30 may be a potential target for the treatment of cervical cancer. The relative high expression of GPR30 in patients suggests that estrogen supplement therapy for postmenopausal women should be considered carefully. The main problem in this study is that the number of cases is relatively small, because for many phenomena, only a certain tendency can be suggested but not enough to come to a definite conclusion. In the future study, the sample size should be expanded on the one hand, and the other is to expand the sample size in the future. On the one hand, specimens of cervical intraepithelial neoplasia (CIN) should be supplemented, and the prognosis of patients with GPR30 positive cervical cancer can be examined by long-term follow-up, providing more guidance for clinical practice.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R737.33
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本文编号：1950788