Claudin-7、E-cadherin和MMP-7在乳腺浸润性导管癌中的表达及其临床意义

发布时间：2018-04-13 17:26

本文选题：乳腺浸润性导管癌 + Claudin-7　；参考：《河北医科大学》2015年硕士论文

【摘要】：目的:乳腺癌是危害女性健康最常见的恶性肿瘤,近年来,其发病率在我国呈现出较快的增长趋势。乳腺浸润性导管癌是女性乳腺癌中最常见的病理类型,约占70%以上。尽管乳腺癌的总体预后较好,但仍有部分患者因术后转移而死亡,因此有必要深入研究乳腺癌细胞发生、发展、浸润、转移的分子生物学机制,了解其生物学行为,在此基础上寻找新的治疗靶点或策略。大量研究表明,乳腺癌的发生、浸润、转移是一个多因素参与,分阶段、分步骤的复杂的级联式反应过程,多数学者支持肿瘤浸润和转移的脱落、黏附、降解和移动四步学说。紧密连接蛋白Claudin-7作为Claudins家族成员,其潜在作用在于限制支持癌细胞的营养和生长因子的供应,在癌组织中失去紧密连接蛋白Claudins在膜上的定位是肿瘤细胞脱落移位的关键步骤。E-cadherin(E-cad)在促进细胞间黏附,维持细胞极性,稳定细胞结构中具有重要作用。MMP-7在肿瘤发生、发展过程中,不仅能够降解细胞外基质,还可以促进肿瘤血管形成。因此,在肿瘤的形成、发展、浸润、转移过程中,Claudin-7、E-cad和MMP-7可能起到了至关重要的作用。本研究拟联合检测Claudin-7、E-cad和MMP-7在乳腺浸润性导管癌组织中的表达,分析三者的表达与肿瘤细胞发生、发展、浸润、转移的关系,并探讨它们在乳腺浸润性导管癌中的相互作用机制,为判断乳腺癌的预后提供理论基础。方法:本研究共收集2013年10月至2014年10月沧州市中心医院肿瘤外科经治的192例乳腺癌病理资料,其中乳腺浸润性导管癌157例,乳腺导管原位癌35例,另取癌旁5cm乳腺组织30例作为对照。所有乳腺癌患者均排除了术前实施过化疗、放疗及其他治疗。我们将每个乳腺组织蜡块切成厚度4μm的连续切片7张,1张切片用于常规HE染色来观察病理形态学,另外6张分别用于免疫组织化学SP染色方法来观察Claudin-7、E-cad和MMP-7的表达情况,并对Claudin-7、E-cad和MMP-7在乳腺浸润性导管癌中的表达与临床病理特征的关系进行了探讨。应用spss13.0统计软件进行数据分析。统计方法包括?2检验、fisher确切概率法、kruskal-wallish检验、wilcoxon秩和检验、spearman等级相关分析等。检验标准以p0.05差异有统计学意义。结果:1claudin-7在癌旁乳腺组织、乳腺导管原位癌、乳腺浸润性导管癌中的阳性表达分别为93.33%、37.14%、23.57%(p0.05),有统计学意义;e-cad在癌旁乳腺组织、乳腺导管原位癌、乳腺浸润性导管癌中的阳性表达分别为86.67%、48.57%、34.39%(p0.05),有统计学意义;mmp-7在癌旁乳腺组织、乳腺导管原位癌、乳腺浸润性导管癌中的阳性表达分别为23.33%42.86%、73.89%(p0.05),有统计学意义。2claudin-7、e-cad、mmp-7在乳腺浸润性导管癌中的表达均与临床分期、组织学分级、淋巴结转移及脉管瘤栓有关,有统计学差异(p0.05),claudin-7、e-cad的阳性表达率随着临床分期的增加、组织学分级的增高、淋巴结的转移、脉管瘤栓的出现而降低,而mmp-7的阳性表达率则升高。claudin-7、e-cad、mmp-7在乳腺浸润性导管癌中的表达与患者的年龄,是否绝经无关,无统计学差异(p0.05);e-cad、mmp-7在乳腺浸润性导管癌中的表达与肿瘤大小无关,无统计学差异(p0.05),而claudin-7乳腺浸润性导管癌中的表达与肿瘤大小有关,有统计学差异(p0.05),随肿瘤直径的增大其表达降低。3应用spearman等级相关分析对claudin-7蛋白、e-cad蛋白、mmp-7蛋白表达状况进行两两进行相关性检验,结果表明,乳腺浸润性导管癌患者中claudin-7蛋白与e-cad蛋白的表达呈正相关(r=0.261,p=0.001),mmp-7蛋白与e-cad蛋白、claudin-7蛋白的表达均无明显相关关系(r=-0.119,p=0.138;r=-0.148,p=0.064)。结论:1与癌旁乳腺组织相比,claudin-7、e-cad在癌组织中表达降低;而mmp-7在癌组织中呈高表达。2claudin-7、e-cad、mmp-7在乳腺浸润性导管癌中的表达均与临床分期、组织学分级、淋巴结转移及脉管瘤栓有关,claudin-7、e-cad的阳性表达率随着临床分期的增加、组织学分级的增高、淋巴结的转移、脉管瘤栓的出现而降低,Claudin-7乳腺浸润性导管癌中的表达还与肿瘤大小有关;而MMP-7的阳性表达率则升高。提示Claudin-7、E-cad的阳性表达的缺失及MMP-7的阳性表达增加促进了乳腺癌的进展,可能与乳腺癌的预后不良有关。3在乳腺浸润性导管癌中,Claudin-7的表达与E-cad的表达呈正相关,MMP-7的表达与Claudin-7、E-cad的表达均无相关性,提示Claudin-7和E-cad可能协同促进乳腺浸润性导管癌的发展,而MMP-7可能作为一个独立的因素参与乳腺浸润性导管癌的发展。
[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.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.9

【参考文献】