醫(yī)學(xué)免費(fèi)論文:基質(zhì)金屬蛋白酶-3、10在子宮內(nèi)膜腺癌組織中的表達(dá)
【摘要】 目的 了解基質(zhì)金屬蛋白酶-3、10(MMP-3、MMP-10)在子宮內(nèi)膜腺癌組織中的表達(dá)情況,及與病變的浸潤(rùn)程度、組織學(xué)分級(jí)、臨床分期等方面的關(guān)系,探討MMP-3、MMP-10在子宮內(nèi)膜癌的發(fā)病、浸潤(rùn)和轉(zhuǎn)移中的作用及意義。方法 采用免疫組織化學(xué)方法分別檢測(cè)42例子宮內(nèi)膜癌、12例非典型增生、12例正常子宮內(nèi)膜組織中MMP-3、MMP-10的表達(dá),并進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果 本實(shí)驗(yàn)結(jié)果顯示,子宮內(nèi)膜腺癌、子宮內(nèi)膜不典型增生過(guò)長(zhǎng)和正常子宮內(nèi)膜組織中MMP-3陽(yáng)性表達(dá)率分別為73.8%(31/42)、25.0%(3/12)、8.3%(1/12),MMP-10陽(yáng)性表達(dá)率分別為76.2%(32/42)、33.3%(4/12)、0%(0/12)。MMP-3、MMP-10的表達(dá)均呈逐漸下降趨勢(shì),每?jī)山M的統(tǒng)計(jì)學(xué)檢驗(yàn)顯示,MMP-3、MMP-10在子宮內(nèi)膜腺癌與子宮內(nèi)膜不典型增生過(guò)長(zhǎng)、子宮內(nèi)膜腺癌與正常子宮內(nèi)膜組織之間,均有統(tǒng)計(jì)學(xué)差異(P<0.01);;MMP-3、MMP-10的表達(dá)與組織學(xué)分級(jí)、肌層浸潤(rùn)程度、臨床分期均有關(guān)(P<0.01);MMP-3、MMP-10在子宮內(nèi)膜腺癌中的表達(dá)有明顯相關(guān)性(P<0.01),聯(lián)合檢測(cè)MMP-3、MMP-10可提高子宮內(nèi)膜腺癌的檢出率。結(jié)論 MMP-3與MMP-10可作為子宮內(nèi)膜腺癌的腫瘤標(biāo)志物之一,且聯(lián)合檢測(cè)MMP-3與MMP-10可提高子宮內(nèi)膜腺癌的檢出率。
【關(guān)鍵詞】 子宮內(nèi)膜腺癌;基質(zhì)金屬蛋白酶-3;基質(zhì)金屬蛋白酶-10醫(yī).學(xué)全.在.線網(wǎng)站bhskgw.cn
Expressions of matrix metalloproteinase-3 and matrix metalloproteinase-10 in endometrial carcinomaFENG Jun, GOU Wen-li, LIU Dan, LI XuDepartment of Peripheral Angiography; Department of Gynecology & Obstetrics;Center of Molecule Experiment, the FirstAffiliated Hospital Medical School of Xian Jiaotong University, Xian 710061, ChinaABSTRACT: Objective To explore the expression of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-10 (MMP-10) in normal endometrium, atypical hyperplasia and endometrial adenocarcinoma. We aimed to study the relationship of MMP-3 and MMP-10 expressions with infiltration depth, histologic grade and clinical phase in order to explore the role of MMP-3 and MMP-10 in the occurrence, infiltration and metastasis of endometrial adenocarcinoma. Methods The expressions of MMP-3 and MMP-10 were measured by immunohistochemistry in 12 cases of normal endometrium, 12 cases of atypical hyperplasia and 42 cases of endometrial adenocarcinoma. Results The expression of MMP-3 was 73.8% (31/42), 25.0% (3/12) and 8.3% (1/12) in endometrial adenocarcinoma, atypical hyperplasia and normal endometrium, respectively, whereas the expression of MMP-10 was 76.2% (32/42), 33.3% (4/12) and 0(0/12), respectively. Both MMP-3 and MMP-10 expressions exhibited a pattern of decreased intensity in endometrial carcinoma, atypical hyperplasia and normal endometrium. Furthermore, the statistical analysis showed that the expression of both proteins was significantly greater in endometrial carcinoma than in atypical hyperplasia and normal tissue (P<0.01). Expressions of MMP-3 and MMP-10 had a significant correlation with such clinical parameters as histologic grade, depth of myometrial infiltration and clinical stage (P<0.01). Conclusion MMP-3 and MMP-10 can be used as tumor markers of endometrial carcinoma, and the combined detection of them can increase the detection rate of endometrial carcinoma.
KEY WORDS: endometrial carcinoma; matrix metalloproteinase-3; matrix metalloproteinase-10
惡性腫瘤侵襲和轉(zhuǎn)移的先決條件是細(xì)胞外基質(zhì)(extracellular matrix, ECM)的降解。ECM是由膠原、蛋白多糖及糖蛋白等成分構(gòu)成的細(xì)胞外骨架結(jié)構(gòu)。基質(zhì)的降解和基底膜的重塑及穿出血管壁進(jìn)入微環(huán)境的過(guò)程,對(duì)于癌細(xì)胞侵襲轉(zhuǎn)移過(guò)程來(lái)說(shuō)是關(guān)鍵環(huán)節(jié)。研究表明,癌細(xì)胞可產(chǎn)生大量分解酶降解基質(zhì)或基底膜。這些分解酶與癌侵襲轉(zhuǎn)移能力顯著相關(guān);|(zhì)金屬蛋白酶(matrix metalloproteinase, MMPs)是一組調(diào)節(jié)復(fù)雜的,鋅離子依賴性的內(nèi)肽酶,是一多基因家族,是人體內(nèi)降解ECM的主要酶類,是一類與腫瘤浸潤(rùn)和轉(zhuǎn)移密切相關(guān)的生物酶。MMPs 可以通過(guò)降解ECM、調(diào)節(jié)細(xì)胞凋亡、增加細(xì)胞黏附能力、促進(jìn)新血管生成來(lái)促進(jìn)腫瘤細(xì)胞的生長(zhǎng)、侵襲和轉(zhuǎn)移,從而參與腫瘤演進(jìn)等眾多生理和病理過(guò)程[1];|(zhì)溶解素是MMPs中非常重要的一個(gè)種類,包括MMP-3、MMP-7、MMP-10、MMP-11等,可以降解ECM的主要結(jié)構(gòu),包括Ⅳ、Ⅴ、Ⅸ型膠原、纖維連接蛋白、層粘蛋白、蛋白多糖等。目前,對(duì)基質(zhì)溶解素在腫瘤侵襲與轉(zhuǎn)移中的作用研究較少,尤其是基質(zhì)溶解素-1(MMP-3)、基質(zhì)溶解素-2(MMP-10)在子宮內(nèi)膜癌中的作用國(guó)內(nèi)外報(bào)道罕見(jiàn)。因此,探討子宮內(nèi)膜癌組織中MMP-3、MMP-10的表達(dá)及其相關(guān)性具有一定的創(chuàng)新性和實(shí)用性。本研究應(yīng)用免疫組化方法檢測(cè)正常子宮內(nèi)膜、不典型增生子宮內(nèi)膜和子宮內(nèi)膜腺癌組織中MMP-3和MMP-10的蛋白表達(dá)情況,以及其表達(dá)變化與組織學(xué)分級(jí)、肌層浸潤(rùn)程度、臨床分期的關(guān)系,并結(jié)合臨床病理特征,初步探討MMP-3和MMP-10與子宮內(nèi)膜腺癌發(fā)生、發(fā)展的關(guān)系及其臨床意義。