本文選題：宮頸癌 + 雌激素受體　； 參考：《北京協(xié)和醫(yī)學院》2015年博士論文

【摘要】：宮頸癌是女性常見的惡性腫瘤,在生殖系統(tǒng)腫瘤中占首位。我國女性中,宮頸癌的發(fā)病率僅次于乳腺癌而在惡性腫瘤中居于第二位,嚴重影響女性健康。宮頸癌的發(fā)生于人乳頭瘤病毒(HPV)的感染有明確的相關性。正常宮頸從HPV感染到發(fā)生癌變需要經(jīng)過漫長的過程,因此,期間應該還受到其他因素的影響。雌激素是人體內(nèi)重要的性激素,與女性正常生理功能的發(fā)育和維持中都起到重要作用,同時也是導致多種女性惡性腫瘤發(fā)生的危險因素。關于雌激素對乳腺癌、子宮內(nèi)膜癌影響的研究已有很多。但其與宮頸癌的關系,許多研究還沒有明確定論。但人們已經(jīng)認識到,雌激素對宮頸癌的發(fā)生和預后都具有一定的影響。雌激素在細胞內(nèi)起作用的方式主要是與雌激素受體結(jié)合。研究較多的是雌激素受體(ER),近年來,雌激素的另一種受體G蛋白偶聯(lián)受體30(GPR30)也逐漸受到重視。GPR30是一種主要定位于細胞器的跨膜蛋白,它與雌激素結(jié)合之后主要通過非基因組途徑,激活下游EGF/MAPK等信號轉(zhuǎn)導通路而發(fā)揮作用。GPR30可能在腫瘤的發(fā)生發(fā)展中發(fā)揮作用,但關于其在宮頸癌組織中的表達與功能,尚無明確報道。本文中,我們收集了宮頸癌患者組織標本；同時以因良性病變行子宮切除術的正常宮頸組織作為對照,各計37例。我們采用對病理切片進行免疫組化染色的方法,考察正常宮頸組織和宮頸癌組織中雌激素的兩種受體ER、GPR30的表達水平。在37例正常宮頸組織中,ER的陽性率100%,GPR30陽性率16.2%； 37例宮頸癌組織中,ER的陽性率27%,GPR30陽性率51.3%。宮頸癌組織中,ER的表達明顯低于對照組,而GPR30的表達明顯升高。我們進一步分析GPR30表達與宮頸癌患者臨床指標的關系。GPR30(+)在絕經(jīng)患者中的比例高于未絕經(jīng)患者,其在中至高分化的宮頸癌中比例較高。而在臨床分期較高的宮頸癌患者中,GPR30的陽性稍高。GPR30陽性與宮頸癌患者的病理類型未見明顯相關,其與淋巴結(jié)轉(zhuǎn)移的相關性較ER明顯。因此我們可以看出,GPR30在宮頸癌組織中的表達明顯高于對照組,這提示了GPR30的異�；罨龠M宮頸癌發(fā)生的可能性。結(jié)合臨床,我們認為GPR30有可能作為治療宮頸癌的潛在靶點。同時,絕經(jīng)后宮頸癌患者GPR30的相對高表達,提示對于這部分患者的絕經(jīng)后雌激素補充療法應予慎重考慮。本研究的主要問題是病例數(shù)相對較少,因為對于許多現(xiàn)象,僅能提示某種傾向而不足以得出較確實的結(jié)論。在今后的研究中,一方面應擴大樣本量,另一方面也應補充宮頸上皮內(nèi)瘤樣病變(CIN)的標本。同時可以通過長期隨診,考察GPR30陽性的宮頸癌患者的預后情況,為臨床提供更多的指導意義。
[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.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R737.33
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本文編號：1950788