本文關(guān)鍵詞： α-SMA MMP-2 bFGF 宮頸上皮內(nèi)瘤變 宮頸微小浸潤(rùn)癌　出處：《山東大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：研究背景子宮頸癌的發(fā)病率和死亡率在所有女性惡性腫瘤中均位居第4位,而在女性生殖系統(tǒng)惡性腫瘤中高居第2位,稍低于乳腺癌。世界衛(wèi)生組織(WHO)統(tǒng)計(jì)數(shù)據(jù)顯示2012年全球?qū)m頸癌新發(fā)病例約為528,000例,而死亡病例約為266.000例。宮頸癌發(fā)病存在較大的地域差別,新發(fā)病例的70%集中在發(fā)展中國(guó)家;其中我國(guó)新發(fā)病例和死亡病例約占11.7%和11.1%。根據(jù)中國(guó)國(guó)家癌癥中心2015年發(fā)布數(shù)據(jù)顯示,宮頸癌新發(fā)病例和死亡病例預(yù)計(jì)達(dá)98,900例和30.500例,呈明顯上升趨勢(shì),與發(fā)達(dá)國(guó)家相反。所以尋找有效方法篩查出宮頸上皮內(nèi)瘤變(cervical intraepithelial neoplasia,CIN)、宮頸微小浸潤(rùn)癌(microinvasive carcinoma of cervix,MIC)、宮頸浸潤(rùn)性癌患者,根據(jù)臨床指南采取相應(yīng)的治療及隨訪措施,能有效的改善病人預(yù)后,明顯提高生存率和生活質(zhì)量。大量研究顯示,αα-平滑肌肌動(dòng)蛋白(α-SmoothMuscleActin,α-SMA)在多種惡性腫瘤(如乳腺癌、口腔癌、鼻咽癌等)間質(zhì)中的肌纖維母細(xì)胞中有較強(qiáng)的陽(yáng)性表達(dá)�；|(zhì)金屬蛋白酶-2(MatrixMetalloproteinases-2,MMP-2)在宮頸癌、胰腺癌上皮中隨病變級(jí)別的升高表達(dá)上調(diào)。堿性成纖維生長(zhǎng)因子(Basic fibroblast growth factor,bFGF)在宮頸癌、非小細(xì)胞肺癌、乳腺癌、結(jié)腸癌、甲狀腺癌、胃癌上皮中隨病變級(jí)別升高表達(dá)逐漸增強(qiáng)。證實(shí)其在腫瘤的發(fā)生、進(jìn)展中起很重要的作用。但三種抗體在MIC及CINⅢ間質(zhì)中表達(dá)的相關(guān)研究較少。研究目的本研究通過(guò)檢測(cè)α-SMA、MMP-2、b-FGF三種抗體在子宮頸高級(jí)別上皮內(nèi)瘤變(CINⅢ)、宮頸微小浸潤(rùn)癌和正常對(duì)照宮頸間質(zhì)中的表達(dá),探討其在腫瘤發(fā)生、發(fā)展中表達(dá)的差異及CINⅢ與MIC鑒別診斷中的意義。資料來(lái)源與方法收集山東大學(xué)齊魯醫(yī)院和東阿縣人民醫(yī)院2008年01月至2015年10月共110例全子宮切除或?qū)m頸錐形切除的標(biāo)本,選取因子宮平滑肌瘤或子宮腺肌病而切除子宮的正常宮頸組織作為對(duì)照,對(duì)照組、CINⅢ組、MIC組分別選取30例、50例、30例樣本行免疫組化檢測(cè),免疫組化采用通用二步法檢測(cè)三組樣本的間質(zhì)細(xì)胞中α-SMA、MMP-2、bFGF抗體的表達(dá)。所有病例的組織學(xué)切片及免疫組化切片均經(jīng)兩位高年資病理主治醫(yī)師共同閱片、判讀,應(yīng)用Greenspan半定量法對(duì)染色強(qiáng)度及著色百分率綜合評(píng)判。應(yīng)用SPSS18.0統(tǒng)計(jì)分析軟件處理數(shù)據(jù)。等級(jí)資料用例數(shù)和百分比表示。組間比較采用非參數(shù)統(tǒng)計(jì)的H檢驗(yàn)。α-SMA和MMP-2指標(biāo)間相關(guān)性分析采用Spearman相關(guān)分析,P≤0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果α-SMA在CIN Ⅲ組和MIC組的腫瘤細(xì)胞周?chē)g質(zhì)中的纖維母細(xì)胞彌漫陽(yáng)性表達(dá),在對(duì)照組中無(wú)表達(dá),表達(dá)的差異具有統(tǒng)計(jì)學(xué)意義(X2=55.14,P0.001)。MMP-2主要定位于胞質(zhì),在對(duì)照組、CIN Ⅲ組和MIC組間質(zhì)的成纖維細(xì)胞中表達(dá)的陽(yáng)性率逐漸升高且表達(dá)逐漸增強(qiáng),差異具統(tǒng)計(jì)學(xué)意義(X2=51.90,P0.001)。bFGF蛋白陽(yáng)性反應(yīng)產(chǎn)物主要位于胞質(zhì),隨著疾病程度的進(jìn)展,其陽(yáng)性表達(dá)率逐漸上升,各組間的表達(dá)率存在顯著差異(X2=13.40,P0.001),但表達(dá)以弱陽(yáng)為主,提示其敏感性不如前兩種抗體。采用Spearman等級(jí)相關(guān)性分析,間質(zhì)中MMP-2的表達(dá)與a-SMA的表達(dá)存在低度正相關(guān)(rs=0.324,p0.05)。結(jié)論α-SMA、MMP-2、bFGF在對(duì)照組、CINⅢ組、MIC組間質(zhì)中表達(dá)差異有統(tǒng)計(jì)學(xué)意義(P0.001)。間質(zhì)細(xì)胞中MMP-2與α-SMA表達(dá)存在低度正相關(guān)(rs=0.324,p0.05)。可聯(lián)合應(yīng)用于MIC的診斷及鑒別診斷。
[Abstract]:The research background of cervical cancer incidence and mortality ranked fourth in all female malignant tumors, and in female genital malignant tumors ranked second, slightly lower than breast cancer. WHO (WHO) statistics show that in 2012 the global cervical cancer new cases is about 528000 cases and death cases is about 266 cases there is regional difference. The incidence of cervical cancer, 70% of new cases concentrated in developing countries; the Chinese new cases and deaths accounted for 11.7% and 11.1%. China according to the National Cancer Center in 2015 released data show that new cases of cervical cancer cases and deaths is expected to reach 98900 cases and 30.500 cases showed an increasing trend. In contrast with the developed countries. So the effective methods for the screening of cervical intraepithelial neoplasia (cervical intraepithelial, neoplasia, CIN), micro invasive cervical cancer (microinvasive carcinoma of CE Rvix, MIC), invasive cervical cancer patients, according to clinical guidelines for treatment and follow-up take corresponding measures, can effectively improve the prognosis of patients, improve the survival rate and quality of life. Many studies show that alpha smooth muscle actin (alpha -SmoothMuscleActin, alpha -SMA) in a variety of malignant tumors (such as breast cancer, oral cancer nasopharyngeal carcinoma, etc.) have strong positive expression in the stroma of myofibroblasts. Matrix metalloproteinase -2 (MatrixMetalloproteinases-2, MMP-2) in cervical cancer, pancreatic cancer with elevated levels of epithelial lesions. The upregulation of the expression of basic fibroblast growth factor (Basic fibroblast, growth factor, bFGF) in cervical carcinoma, non-small cell lung cancer, breast cancer, colorectal cancer, thyroid cancer, gastric epithelial lesions with elevated expression level gradually. Prove the tumor plays an important role in progress. But the three kinds of antibodies in MIC and CIN between 3 Less relevant research in expression. This study through the detection of alpha -SMA, MMP-2, b-FGF three kinds of antibodies in cervical intraepithelial neoplasia (CIN III), microinvasive carcinoma and normal cervical stroma expression in cervical tumorigenesis, explore the significance of differential diagnosis, differential expressed and CIN 3 and in MIC development. Data sources and methods in 2008 in Qilu Hospital and Dong'e County People's Hospital of Shandong University from 01 to October 2015 a total of 110 cases of cervical conization or hysterectomy specimens, select normal cervical tissue due to uterine leiomyoma or adenomyosis uterus disease as the control group, the control group, CIN in group III, MIC group of 30 cases were selected, 50 cases, 30 cases of the immunohistochemical staining, immunohistochemistry using general two step method for detection of three samples of interstitial cells in the alpha -SMA, MMP-2, bFGF expression in tissues of all cases antibodies. Biopsy and immunohistochemical sections were confirmed by two senior pathologist read, interpretation, application of Greenspan semi quantitative method of staining intensity and staining percentage of comprehensive evaluation. The application of SPSS18.0 statistical analysis software to process data. Rank data case number and percentage. The groups were compared using H test and nonparametric statistics. Spearman correlation analysis was used for correlation analysis of alpha -SMA and MMP-2 index, P = 0.05, there was statistically significant difference. The alpha -SMA around CIN III and MIC groups of tumor cells in the stroma of fibroblasts with positive expression, no expression in the control group, with statistically significant differences (X2=55.14, P0.001 expression.MMP-2) mainly located in the cytoplasm and in the control group, CIN group and MIC group of interstitial fibroblasts expressing the positive rate gradually increased and the expression gradually increased, the difference was statistically significant (X2= 51.90, P0.00 1).BFGF protein positive reaction product was mainly located in the cytoplasm, with the degree of disease, the positive expression rate gradually increased, the expression rate between groups were significant differences (X2=13.40, P0.001), but the expression to weak positive, suggesting that the sensitivity is not as good as the first two antibody. Spearman correlation analysis is adopted, there is low relative expression of a-SMA and MMP-2 in the stroma of the (rs=0.324, P0.05). Conclusion MMP-2 alpha -SMA, bFGF in the control group, CIN group, MIC group, the expression in the stroma of the difference was statistically significant (P0.001). Interstitial cells of MMP-2 and -SMA expression has positive correlation (rs=0.324, P0.05). The diagnosis and differential diagnosis can be combined with MIC.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33

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