α-SMA、MMP-2、bFGF在子宫颈微小浸润癌间质中的表达与意义

发布时间：2018-01-22 01:21

本文关键词： α-SMA MMP-2 bFGF 宫颈上皮内瘤变宫颈微小浸润癌　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景子宫颈癌的发病率和死亡率在所有女性恶性肿瘤中均位居第4位,而在女性生殖系统恶性肿瘤中高居第2位,稍低于乳腺癌。世界卫生组织(WHO)统计数据显示2012年全球宫颈癌新发病例约为528,000例,而死亡病例约为266.000例。宫颈癌发病存在较大的地域差别,新发病例的70%集中在发展中国家;其中我国新发病例和死亡病例约占11.7%和11.1%。根据中国国家癌症中心2015年发布数据显示,宫颈癌新发病例和死亡病例预计达98,900例和30.500例,呈明显上升趋势,与发达国家相反。所以寻找有效方法筛查出宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)、宫颈微小浸润癌(microinvasive carcinoma of cervix,MIC)、宫颈浸润性癌患者,根据临床指南采取相应的治疗及随访措施,能有效的改善病人预后,明显提高生存率和生活质量。大量研究显示,αα-平滑肌肌动蛋白(α-SmoothMuscleActin,α-SMA)在多种恶性肿瘤(如乳腺癌、口腔癌、鼻咽癌等)间质中的肌纤维母细胞中有较强的阳性表达。基质金属蛋白酶-2(MatrixMetalloproteinases-2,MMP-2)在宫颈癌、胰腺癌上皮中随病变级别的升高表达上调。碱性成纤维生长因子(Basic fibroblast growth factor,bFGF)在宫颈癌、非小细胞肺癌、乳腺癌、结肠癌、甲状腺癌、胃癌上皮中随病变级别升高表达逐渐增强。证实其在肿瘤的发生、进展中起很重要的作用。但三种抗体在MIC及CINⅢ间质中表达的相关研究较少。研究目的本研究通过检测α-SMA、MMP-2、b-FGF三种抗体在子宫颈高级别上皮内瘤变(CINⅢ)、宫颈微小浸润癌和正常对照宫颈间质中的表达,探讨其在肿瘤发生、发展中表达的差异及CINⅢ与MIC鉴别诊断中的意义。资料来源与方法收集山东大学齐鲁医院和东阿县人民医院2008年01月至2015年10月共110例全子宫切除或宫颈锥形切除的标本,选取因子宫平滑肌瘤或子宫腺肌病而切除子宫的正常宫颈组织作为对照,对照组、CINⅢ组、MIC组分别选取30例、50例、30例样本行免疫组化检测,免疫组化采用通用二步法检测三组样本的间质细胞中α-SMA、MMP-2、bFGF抗体的表达。所有病例的组织学切片及免疫组化切片均经两位高年资病理主治医师共同阅片、判读,应用Greenspan半定量法对染色强度及着色百分率综合评判。应用SPSS18.0统计分析软件处理数据。等级资料用例数和百分比表示。组间比较采用非参数统计的H检验。α-SMA和MMP-2指标间相关性分析采用Spearman相关分析,P≤0.05为差异有统计学意义。结果α-SMA在CIN Ⅲ组和MIC组的肿瘤细胞周围间质中的纤维母细胞弥漫阳性表达,在对照组中无表达,表达的差异具有统计学意义(X2=55.14,P0.001)。MMP-2主要定位于胞质,在对照组、CIN Ⅲ组和MIC组间质的成纤维细胞中表达的阳性率逐渐升高且表达逐渐增强,差异具统计学意义(X2=51.90,P0.001)。bFGF蛋白阳性反应产物主要位于胞质,随着疾病程度的进展,其阳性表达率逐渐上升,各组间的表达率存在显著差异(X2=13.40,P0.001),但表达以弱阳为主,提示其敏感性不如前两种抗体。采用Spearman等级相关性分析,间质中MMP-2的表达与a-SMA的表达存在低度正相关(rs=0.324,p0.05)。结论α-SMA、MMP-2、bFGF在对照组、CINⅢ组、MIC组间质中表达差异有统计学意义(P0.001)。间质细胞中MMP-2与α-SMA表达存在低度正相关(rs=0.324,p0.05)。可联合应用于MIC的诊断及鉴别诊断。
[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.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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