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MCM5蛋白在子宮內(nèi)膜癌中的表達(dá)及臨床意義

發(fā)布時(shí)間:2018-04-09 23:05

  本文選題:子宮內(nèi)膜癌 切入點(diǎn):子宮內(nèi)膜不典型增生 出處:《承德醫(yī)學(xué)院》2014年碩士論文


【摘要】:子宮內(nèi)膜癌是最常見的婦科惡性腫瘤之一,它是產(chǎn)生于子宮內(nèi)膜的一組上皮性惡性腫瘤,在其多種不同起源的腫瘤中,以子宮內(nèi)膜腺體的腺癌最常見。在我國(guó),雖然其發(fā)病率和死亡率沒有統(tǒng)計(jì)數(shù)據(jù)更準(zhǔn)確的描述的子宮內(nèi)膜癌,但至少我們可以通過報(bào)道,了解到該病的發(fā)生率每年都在增加,而且死亡率很高。所以,有必要明確一些和子宮內(nèi)膜癌發(fā)生、發(fā)展有關(guān)的問題,了解一些與腫瘤相關(guān)的組織學(xué)變化,并根據(jù)子宮內(nèi)膜腫瘤細(xì)胞異常增殖,及其轉(zhuǎn)移機(jī)制和對(duì)周圍組織的侵襲,就可以相對(duì)準(zhǔn)確的判斷腫瘤的風(fēng)險(xiǎn)評(píng)估及預(yù)后,以及制定更有效的治療方案,提高子宮內(nèi)膜癌的療效、改善患者生活質(zhì)量。 微小染色體維持蛋白(Miniehromosome Maintenance Proteins)是一組蛋白, DNA復(fù)制與其密切相關(guān)。是二十世紀(jì)80年代Bik-kwoon tye,在突變酵母中發(fā)現(xiàn),然后運(yùn)用分子和生物化學(xué)的實(shí)驗(yàn)方法提取出來的,是一組重要的同源蛋白家族,并且它們之間關(guān)聯(lián)密切。微小染色體維持蛋白(McMs)在復(fù)制準(zhǔn)許因子,RLF)中起著重要的作用,是DNA復(fù)制的一個(gè)重要成員,它在DNA復(fù)制起始前就與染色質(zhì)結(jié)合,是一個(gè)新的復(fù)制過程開始的標(biāo)志。RLF這個(gè)復(fù)合物是DNA復(fù)制的一個(gè)“通行證”,在真核細(xì)胞的DNA復(fù)制過程中有著無可替代的重要性。在真核細(xì)胞DNA復(fù)制過程中,MCM蛋白是這個(gè)過程中重要的調(diào)節(jié)蛋白,而DNA復(fù)制的異常調(diào)節(jié)又導(dǎo)致了細(xì)胞異常增殖。MCM蛋白在靜止期或分化較好的細(xì)胞中很少表達(dá)或不表達(dá),而在增殖細(xì)胞中高水平表達(dá)。由此可見MCM蛋白可以成為一種增殖細(xì)胞的特異性標(biāo)志物。而MCM5是MCM蛋白家族中的六個(gè)成員之一,也就是說,檢測(cè)MCM5的表達(dá)就可間接了解MCM蛋白的表達(dá)水平。因此,MCM5蛋白腫瘤研究過程中,結(jié)合患者臨床資料,證實(shí)其與惡性腫瘤的病理分期、淋巴轉(zhuǎn)移及預(yù)后評(píng)估有相關(guān)性,成為有價(jià)值的標(biāo)記物。 本課題通過對(duì)手術(shù)切除的子宮內(nèi)膜癌標(biāo)本進(jìn)行檢測(cè),運(yùn)用免疫組化方法,了解MCM5蛋白在子宮內(nèi)膜癌組織中的表達(dá),并將其與MCM5在不典型增生的內(nèi)膜組織及正常子宮內(nèi)膜組織進(jìn)行比較,并結(jié)合患者臨床資料,分析MCM5蛋白在子宮內(nèi)膜癌發(fā)生發(fā)展中的表達(dá)特點(diǎn),從而為子宮內(nèi)膜癌惡性程度判斷和子宮內(nèi)膜癌的預(yù)后評(píng)估提供新的新的腫瘤標(biāo)記物。 目的: 通過對(duì)子宮內(nèi)膜癌標(biāo)本進(jìn)行免疫組織化學(xué)染色方法,檢測(cè)子宮內(nèi)膜癌中MCM5蛋白的表達(dá),與不典型增生子宮內(nèi)膜組織、正常子宮內(nèi)膜組織進(jìn)行對(duì)比,并同時(shí)結(jié)合患者臨床資料,分析MCM5蛋白在子宮內(nèi)膜癌的發(fā)生發(fā)展中,其表達(dá)的特點(diǎn),從而為判斷子宮內(nèi)膜癌惡性程度及其預(yù)后評(píng)估提供新的方法。 方法: 選取保定市二醫(yī)院、承德醫(yī)學(xué)院附屬醫(yī)院,經(jīng)手術(shù)切除標(biāo)本,并且所有標(biāo)本經(jīng)病理證實(shí)為子宮內(nèi)膜癌70例(通過2年的術(shù)后隨訪,其中復(fù)發(fā)患者29例,同期對(duì)照無復(fù)發(fā)患者有41例)。70例癌的組織學(xué)類型均為子宮內(nèi)膜樣腺癌,無透明細(xì)胞癌、漿液性癌等特殊組織學(xué)類型腫瘤。所有患者術(shù)前均未經(jīng)任何其他特殊治療,例如化療、放療及藥物,記錄患者姓名、年齡、病理分期(根據(jù)2009年FIGO分期)、腫瘤分化程度,免疫組化結(jié)果、有無淋巴結(jié)轉(zhuǎn)移等臨床資料,另選擇正常子宮內(nèi)膜組織標(biāo)本15例和同期不典型增生組織21例作為對(duì)照。采用免疫組織化學(xué)S-P法檢測(cè)所選標(biāo)本中MCM5蛋白的表達(dá)。應(yīng)用統(tǒng)計(jì)學(xué)軟件SPSS for windows14.0,通過等級(jí)資料的秩和檢驗(yàn)和χ2檢驗(yàn)分析,MCM5蛋白與子宮內(nèi)膜腺癌的關(guān)系。 結(jié)果: 1.應(yīng)用免疫組化S-P法檢測(cè)子宮內(nèi)膜癌組織、不典型增生子宮內(nèi)膜組織、正常子宮內(nèi)膜組織中MCM5蛋白的表達(dá)情況:子宮內(nèi)膜癌和不典型增生子宮內(nèi)膜中總陽性表達(dá)率比較無顯著差異(P0.05),但在強(qiáng)陽性表達(dá)率的比較中,二者的差異有統(tǒng)計(jì)學(xué)意義(P0.05)。 2.子宮內(nèi)膜癌、不典型增生子宮內(nèi)膜中MCM5的表達(dá)比正常子宮內(nèi)膜更廣泛,且具有顯著性差異(P0.05)。 結(jié)論: 1. MCM5蛋白在子宮內(nèi)膜癌組織中是否高度表達(dá),與腫瘤的分化程度、分期、是否有淋巴結(jié)轉(zhuǎn)移密切相關(guān),MCM5在不典型增生子宮內(nèi)膜組織中表達(dá)也明顯高于正常組織。 2. MCM5蛋白在子宮內(nèi)膜癌組織中高度表達(dá),,且與子宮內(nèi)膜癌的預(yù)后評(píng)估相關(guān)。
[Abstract]:Endometrial carcinoma is one of the most common gynecologic malignant tumor, it is a group produced in the endometrial epithelial malignant tumors, in the different origin of tumors, endometrial gland carcinoma is the most common. In our country, although the incidence and mortality of no statistical data of endometrial cancer more accurately the description, but at least we can understand to the annual report, the incidence of the disease is increasing, but the mortality rate is very high. So, it is necessary to clarify some and endometrial cancer occurrence and development related issues, learn to understand the changes and some tumor related organizations, and according to the abnormal proliferation of endometrial cancer cells, and its transfer mechanism and the surrounding tissue invasion, risk assessment and prognosis of tumors can be judged to be relatively accurate, and develop more effective treatment options, improve the curative effect of endometrial carcinoma and to improve the lives of patients Quality.
Minichromosome maintenance proteins (Miniehromosome Maintenance Proteins) is a group of proteins, DNA replication is closely related. In twentieth Century 80s Bik-kwoon tye, found that mutations in yeast, and then use the experimental method of molecular and biochemical extraction, is an important group of homologous protein family, and they are closely related. Minichromosome maintenance protein (McMs) on the replication licensing factor, RLF) plays an important role, is an important member of DNA replication, it is combined with the chromatin in the initiation of DNA replication, is a new replication marks the beginning of the.RLF complex is a "pass" DNA replication, a the irreplaceable importance in the replication of eukaryotic cells. In the process of DNA replication in eukaryotic cells DNA, MCM protein is an important regulator of this process, and the abnormal regulation of DNA replication and guide Due to the abnormal proliferation of cells.MCM protein in quiescent cell differentiation or better in little or no expression, and high expression levels in proliferating cells. Thus MCM protein can be a specific marker for cell proliferation. MCM5 is one of the six members of the MCM family, that is to say, the expression of the detection of MCM5 can indirectly understand the expression level of MCM protein. Therefore, MCM5 protein in tumor research, combined with the clinical data, confirmed the malignant tumors and pathological staging, lymph node metastasis and prognostic assessment of relevance, become a valuable marker.
This topic through the detection of surgical resection of endometrial cancer specimens by immunohistochemical method, expression of MCM5 protein in endometrial carcinoma, and MCM5 were compared in atypical hyperplasia of endometrium and normal endometrium, and combined with clinical data, analysis of MCM5 protein expression in the characteristics of the occurrence and development of endometrial carcinoma, which provides a new tumor marker for a new assessment of endometrial cancer prognosis judging malignant degree and endometrial cancer.
Objective:
By immunohistochemical staining of endometrial carcinoma, the expression of MCM5 protein in endometrial carcinoma, and atypical hyperplasia of endometrium and normal endometrium were compared, and at the same time combined with the clinical data, analysis of MCM5 protein in the occurrence and development of endometrial cancer, the characteristics of its expression, in order to provide a new method for evaluating the malignancy degree and prognosis of endometrial carcinoma and its prognosis.
Method:
Select the two hospital, Baoding Affiliated Hospital of Chengde Medical College, after surgical resection specimens, and all specimens were confirmed by pathology in 70 cases of endometrial carcinoma (through 2 years of follow-up, including 29 cases of postoperative recurrence in patients with concurrent control, no recurrence in 41 patients).70 cases of cancer histological types were endometrioid adenocarcinomas. No clear cell carcinoma, serous carcinoma and other special histological types of tumor. All patients without any special treatment, such as chemotherapy, radiotherapy and drug, record the patient's name, age, pathological stage (according to the 2009 FIGO staging), tumor differentiation, immunohistochemical findings, clinical data of lymph node transfer, the other normal endometrial tissue specimens and 15 patients with atypical hyperplasia in 21 cases as control. The expression of MCM5 protein in detection of selected specimens by immunohistochemical S-P method. Using statistical software SPSS for W Indows14.0, the relationship between MCM5 protein and endometrial adenocarcinoma was analyzed by rank sum test and chi 2 test.
Result錛

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