本文選題：乳腺浸潤性導(dǎo)管癌 + Claudin-7��； 參考：《河北醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:乳腺癌是危害女性健康最常見的惡性腫瘤,近年來,其發(fā)病率在我國呈現(xiàn)出較快的增長趨勢。乳腺浸潤性導(dǎo)管癌是女性乳腺癌中最常見的病理類型,約占70%以上。盡管乳腺癌的總體預(yù)后較好,但仍有部分患者因術(shù)后轉(zhuǎn)移而死亡,因此有必要深入研究乳腺癌細(xì)胞發(fā)生、發(fā)展、浸潤、轉(zhuǎn)移的分子生物學(xué)機(jī)制,了解其生物學(xué)行為,在此基礎(chǔ)上尋找新的治療靶點或策略。大量研究表明,乳腺癌的發(fā)生、浸潤、轉(zhuǎn)移是一個多因素參與,分階段、分步驟的復(fù)雜的級聯(lián)式反應(yīng)過程,多數(shù)學(xué)者支持腫瘤浸潤和轉(zhuǎn)移的脫落、黏附、降解和移動四步學(xué)說。緊密連接蛋白Claudin-7作為Claudins家族成員,其潛在作用在于限制支持癌細(xì)胞的營養(yǎng)和生長因子的供應(yīng),在癌組織中失去緊密連接蛋白Claudins在膜上的定位是腫瘤細(xì)胞脫落移位的關(guān)鍵步驟。E-cadherin(E-cad)在促進(jìn)細(xì)胞間黏附,維持細(xì)胞極性,穩(wěn)定細(xì)胞結(jié)構(gòu)中具有重要作用。MMP-7在腫瘤發(fā)生、發(fā)展過程中,不僅能夠降解細(xì)胞外基質(zhì),還可以促進(jìn)腫瘤血管形成。因此,在腫瘤的形成、發(fā)展、浸潤、轉(zhuǎn)移過程中,Claudin-7、E-cad和MMP-7可能起到了至關(guān)重要的作用。本研究擬聯(lián)合檢測Claudin-7、E-cad和MMP-7在乳腺浸潤性導(dǎo)管癌組織中的表達(dá),分析三者的表達(dá)與腫瘤細(xì)胞發(fā)生、發(fā)展、浸潤、轉(zhuǎn)移的關(guān)系,并探討它們在乳腺浸潤性導(dǎo)管癌中的相互作用機(jī)制,為判斷乳腺癌的預(yù)后提供理論基礎(chǔ)。方法:本研究共收集2013年10月至2014年10月滄州市中心醫(yī)院腫瘤外科經(jīng)治的192例乳腺癌病理資料,其中乳腺浸潤性導(dǎo)管癌157例,乳腺導(dǎo)管原位癌35例,另取癌旁5cm乳腺組織30例作為對照。所有乳腺癌患者均排除了術(shù)前實施過化療、放療及其他治療。我們將每個乳腺組織蠟塊切成厚度4μm的連續(xù)切片7張,1張切片用于常規(guī)HE染色來觀察病理形態(tài)學(xué),另外6張分別用于免疫組織化學(xué)SP染色方法來觀察Claudin-7、E-cad和MMP-7的表達(dá)情況,并對Claudin-7、E-cad和MMP-7在乳腺浸潤性導(dǎo)管癌中的表達(dá)與臨床病理特征的關(guān)系進(jìn)行了探討。應(yīng)用spss13.0統(tǒng)計軟件進(jìn)行數(shù)據(jù)分析。統(tǒng)計方法包括?2檢驗、fisher確切概率法、kruskal-wallish檢驗、wilcoxon秩和檢驗、spearman等級相關(guān)分析等。檢驗標(biāo)準(zhǔn)以p0.05差異有統(tǒng)計學(xué)意義。結(jié)果:1claudin-7在癌旁乳腺組織、乳腺導(dǎo)管原位癌、乳腺浸潤性導(dǎo)管癌中的陽性表達(dá)分別為93.33%、37.14%、23.57%(p0.05),有統(tǒng)計學(xué)意義;e-cad在癌旁乳腺組織、乳腺導(dǎo)管原位癌、乳腺浸潤性導(dǎo)管癌中的陽性表達(dá)分別為86.67%、48.57%、34.39%(p0.05),有統(tǒng)計學(xué)意義;mmp-7在癌旁乳腺組織、乳腺導(dǎo)管原位癌、乳腺浸潤性導(dǎo)管癌中的陽性表達(dá)分別為23.33%42.86%、73.89%(p0.05),有統(tǒng)計學(xué)意義。2claudin-7、e-cad、mmp-7在乳腺浸潤性導(dǎo)管癌中的表達(dá)均與臨床分期、組織學(xué)分級、淋巴結(jié)轉(zhuǎn)移及脈管瘤栓有關(guān),有統(tǒng)計學(xué)差異(p0.05),claudin-7、e-cad的陽性表達(dá)率隨著臨床分期的增加、組織學(xué)分級的增高、淋巴結(jié)的轉(zhuǎn)移、脈管瘤栓的出現(xiàn)而降低,而mmp-7的陽性表達(dá)率則升高。claudin-7、e-cad、mmp-7在乳腺浸潤性導(dǎo)管癌中的表達(dá)與患者的年齡,是否絕經(jīng)無關(guān),無統(tǒng)計學(xué)差異(p0.05);e-cad、mmp-7在乳腺浸潤性導(dǎo)管癌中的表達(dá)與腫瘤大小無關(guān),無統(tǒng)計學(xué)差異(p0.05),而claudin-7乳腺浸潤性導(dǎo)管癌中的表達(dá)與腫瘤大小有關(guān),有統(tǒng)計學(xué)差異(p0.05),隨腫瘤直徑的增大其表達(dá)降低。3應(yīng)用spearman等級相關(guān)分析對claudin-7蛋白、e-cad蛋白、mmp-7蛋白表達(dá)狀況進(jìn)行兩兩進(jìn)行相關(guān)性檢驗,結(jié)果表明,乳腺浸潤性導(dǎo)管癌患者中claudin-7蛋白與e-cad蛋白的表達(dá)呈正相關(guān)(r=0.261,p=0.001),mmp-7蛋白與e-cad蛋白、claudin-7蛋白的表達(dá)均無明顯相關(guān)關(guān)系(r=-0.119,p=0.138;r=-0.148,p=0.064)。結(jié)論:1與癌旁乳腺組織相比,claudin-7、e-cad在癌組織中表達(dá)降低;而mmp-7在癌組織中呈高表達(dá)。2claudin-7、e-cad、mmp-7在乳腺浸潤性導(dǎo)管癌中的表達(dá)均與臨床分期、組織學(xué)分級、淋巴結(jié)轉(zhuǎn)移及脈管瘤栓有關(guān),claudin-7、e-cad的陽性表達(dá)率隨著臨床分期的增加、組織學(xué)分級的增高、淋巴結(jié)的轉(zhuǎn)移、脈管瘤栓的出現(xiàn)而降低,Claudin-7乳腺浸潤性導(dǎo)管癌中的表達(dá)還與腫瘤大小有關(guān);而MMP-7的陽性表達(dá)率則升高。提示Claudin-7、E-cad的陽性表達(dá)的缺失及MMP-7的陽性表達(dá)增加促進(jìn)了乳腺癌的進(jìn)展,可能與乳腺癌的預(yù)后不良有關(guān)。3在乳腺浸潤性導(dǎo)管癌中,Claudin-7的表達(dá)與E-cad的表達(dá)呈正相關(guān),MMP-7的表達(dá)與Claudin-7、E-cad的表達(dá)均無相關(guān)性,提示Claudin-7和E-cad可能協(xié)同促進(jìn)乳腺浸潤性導(dǎo)管癌的發(fā)展,而MMP-7可能作為一個獨立的因素參與乳腺浸潤性導(dǎo)管癌的發(fā)展。
[Abstract]:Objective: breast cancer is one of the most common malignant tumor of female health, in recent years, the incidence rate showed a rapid growth trend in our country. The breast invasive ductal carcinoma is the most common pathological type of breast cancer in women, accounting for more than 70%. Although the overall prognosis of breast cancer is good, but there are still some patients death due to postoperative metastasis, so it is necessary to study the breast cancer cells, development, invasion, metastasis, understanding its biological behavior, based on the search for new therapeutic targets or strategies. A large number of studies show that breast cancer occurrence, invasion, metastasis is a multi factor. In stages, the cascade reaction complex process step by step, most scholars support the exfoliated tumor invasion and metastasis, adhesion, degradation and move four step theory. Tight junction protein Claudin-7 as a Claudins family member, is its potential role Limited support supply nutrition and cancer cell growth factor in cancer tissues, loses the positioning of tight junction protein Claudins in membrane is the key step of tumor cell loss.E-cadherin translocation (E-cad) in promoting cell adhesion, cell polarity, the important role of.MMP-7 in tumor cells with stable structure, development process that not only can degrade extracellular matrix, but also can promote tumor angiogenesis. Therefore, in the process of tumorigenesis, development, invasion, metastasis, Claudin-7 process, E-cad and MMP-7 may play a crucial role in this study. The combined detection of Claudin-7, E-cad and MMP-7 in breast invasive ductal carcinoma. Three, analysis of expression and tumor cells, development, invasion, metastasis, and explore their interaction mechanism of infiltrating ductal carcinoma in the breast, for judging the prognosis of breast cancer. For the theoretical basis. Methods: 192 cases of breast cancer and pathological data were collected from October 2013 to October 2014 in Cangzhou Central Hospital tumor after treatment, including 157 cases of invasive ductal carcinoma, 35 cases of ductal carcinoma in situ, another adjacent 5cm breast tissue in 30 cases as control group. All patients with breast cancer were excluded after chemotherapy before surgery, radiotherapy and other treatment. We will each breast tissue blocks into a thickness of 4 mu m 7 serial sections, 1 sections were used to observe the pathological morphology of routine HE staining, the other 6 were used to observe the Claudin-7 SP immunohistochemical staining method, the expression of E-cad and MMP-7, and Claudin-7. The relationship between E-cad and MMP-7 in invasive ductal carcinoma and clinical pathological features in breast were discussed. The application of SPSS13.0 statistical software for data analysis. The statistical methods include 2 test, Fisher exact? The probability method, kruskal-wallish test, Wilcoxon test, Spearman rank correlation analysis. Test standards to P0.05 the difference was statistically significant. Results: 1claudin-7 in breast carcinoma, ductal carcinoma in situ and invasive breast ductal carcinoma positive expression were 93.33%, 37.14%, 23.57% (P0.05), there was statistical significance; E-cad in breast carcinoma, ductal carcinoma in situ and invasive breast ductal carcinoma positive expression were 86.67%, 48.57%, 34.39% (P0.05), there was statistical significance; MMP-7 in breast carcinoma, mammary gland ductal carcinoma in situ and invasive breast ductal carcinoma, the positive expression of 23.33%42.86% 73.89% (respectively. P0.05), there was statistical significance in.2claudin-7, E-cad, MMP-7 in breast invasive ductal carcinoma with clinical stage, histological grade, lymph node metastasis and vascular invasion, there were significant differences (P0.05, claudin-7), The positive expression rate of E-cad increased with the clinical stage, higher histological grade, lymph node metastasis, tumor thrombus appeared decreased, and MMP-7 expression was increased by.Claudin-7, E-cad, MMP-7 in breast infiltrating ductal carcinoma was related with the age, menopause has no significant difference (P0.05); E-cad, MMP-7 in breast infiltrating ductal carcinoma and the expression of tumor size in the independent, no significant difference (P0.05), and claudin-7 expression and tumor size of breast infiltrating ductal carcinoma is related with significant differences (P0.05), with the increase of the diameter of the tumor decreased expression of.3 using Spearman rank correlation analysis the claudin-7 protein, E-cad protein, MMP-7 protein expression was 22 for correlation test, the results show that the positive correlation between the expression of claudin-7 in patients with invasive ductal carcinoma of the breast and E-cad proteins (r=0.261, p=0 .001), MMP-7 protein and E-cad protein were not significantly related to the expression of claudin-7 (r=-0.119, p=0.138; r=-0.148, p=0.064). Conclusion: 1 compared with adjacent breast tissue claudin-7, E-cad expression decreased in cancer tissues; while MMP-7 showed high expression of.2claudin-7 and E-cad in cancer tissues, MMP-7 in breast invasive ductal carcinoma with clinical stage, histological grade, lymph node metastasis and vascular invasion, claudin-7, the positive expression rate of E-cad increased with the clinical stage, higher histological grade, lymph node metastasis, tumor thrombus appeared decreased, invasive ductal carcinoma Claudin-7 is also associated with breast tumor size; the positive rate of MMP-7 expression was increased. The positive expression of Claudin-7, lack of positive expression of E-cad and MMP-7 increased to promote the progression of breast cancer, and breast cancer may be poor prognosis.3 In breast invasive ductal carcinoma, and E-cad expression was positively related to the expression of Claudin-7, Claudin-7 and MMP-7, there was no correlation between the expression of E-cad, suggesting that Claudin-7 and E-cad may work together to promote the development of breast invasive ductal carcinoma, and MMP-7 may serve as an independent factor in invasive ductal carcinoma of the breast.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R737.9

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相關(guān)期刊論文 前1條

1 李燕;秦蓉;王弦;陳宗科;;子宮頸上皮內(nèi)瘤變進(jìn)展過程中Claudin-1、3、4、7的表達(dá)及意義[J];臨床與實驗病理學(xué)雜志;2013年01期

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本文編號：1745488