【作者】 齐广涛；

【导师】 王德华；

【作者基本信息】 天津医科大学 ， 妇产科学， 2009， 硕士

【摘要】 目的宫颈癌是女性常见的恶性肿瘤之一,在全球妇女恶性肿瘤中居第二位,细胞外基质金属蛋白酶诱导因子(extracellulr matrix metalloproteinase inducer,CD147/EMMPRIN)是可以调节基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)的因子之一,本实验通过检测CD147、MMP-2在正常宫颈组织、宫颈上皮内瘤样变(cervical intraepithelial neoplasia,CIN)以及宫颈癌中的表达情况,分析二者与宫颈癌相关临床病理指标的联系,探讨上述指标在宫颈癌发生、发展、浸润、转移中的作用及相互关系,为宫颈癌的诊断和治疗提供一种新的有效指标。方法采用链霉菌抗生物素蛋白-过氧化物酶连结法(即S-P法)免疫组化方法(immunohistochemistry,IHC)检测20例正常宫颈组织、21例CIN组织、59例宫颈癌组织中CD147和MMP-2的表达情况。分析宫颈癌中CD147和MMP-2的表达与临床分期、组织学分级等临床病理指标的相关性,同时对两者在宫颈癌发展过程中的相互关系进行初步研究。结果1.CD147和MMP-2主要在肿瘤组织中表达,在正常组织中也有表达。2.CD147在正常宫颈组织、CIN、宫颈癌组织中的阳性表达率分别为30.0%,81.0%,91.5%,呈逐渐升高的趋势(P<0.05).其中,正常宫颈组与CIN组之间有显著性差异(P<0.05);正常宫颈组与宫颈癌组之间有显著性差异(P<0.05);CIN组与宫颈癌组之间有显著性差异(P<0.05)。3.MMP-2在正常宫颈组织、CIN、宫颈癌组织中的阳性表达率分别为15.0%,38.1%,80.0%,呈现逐渐升高的趋势(P<0.05)。其中,正常宫颈组与CIN组之间无差异显著性(P>0.05);正常宫颈组与宫颈癌组之间差异有显著性(P<0.05);CIN组与宫颈癌组之间有显著性差异(P<0.05)。4.在宫颈癌中,CD147蛋白表达阳性率在有淋巴结转移组高于无淋巴结转移组(x~2=4.138,P<0.05);宫颈癌中CD147的表达与年龄、分期、大体类型、分化程度、组织类型均无关(P>0.05)。5.在宫颈癌中,MMP-2蛋白表达阳性率在FIGO分期Ⅰ～Ⅱa期高于Ⅱb～Ⅳ期(x~2=9.423,P<0.05),有淋巴结转移组高于无淋巴结转移组(x~2=5.019,P<0.05);宫颈癌中MMP-2的表达与年龄、大体类型、分化程度、组织类型均无关(P>0.05)。6.宫颈癌组织中CD147与MMP-2之间呈正相关,相关系数r_s=0.283(P<0.05)。结论CD147和MMP-2在正常宫颈、CIN、宫颈癌中的表达呈逐渐升高趋势;在宫颈癌中,CD147的表达在有淋巴结转移者表达高于无淋巴结转移者;在宫颈癌中,MMP-2的表达在Ⅱb～Ⅳ期高于Ⅰ～Ⅱa期,在有淋巴结转移的宫颈癌病例表达高于无淋巴结转移者;CD147和MMP-2之间有协同作用;提示CD147和MMP-2在宫颈癌的浸润和转移方面起重要作用,联合检测CD147和MMP-2有可能是宫颈癌诊断的标志物和治疗的新靶点,是评估宫颈癌严重程度的新指标。更多还原

【Abstract】 Objective Cervical cancer is a common malignancy among women,ranked second among in the world of women malignant tumors.Extracellulr matrix metalloproteinase inducer(CD147/EMMPRIN) is one of the molecules involved in regulating the expression of matrix metalloproteinases(MMPs).The goal of this study was to analyze the expression levels of CD 147 and MMP-2 in normal cervical tissue,cervical intraepithelial neoplasia(CIN) and cervical carcinoma,and to analyze its relationship with clinicopathological parameters of cervical cancer-related links to explore the above-mentioned target happened in cervical cancer development, invasion and metastasis,for the diagnosis and treatment of cervical cancer to provide a new and effective target.Methods Using streptavidin-biotin-protein - linked peroxidase method(ie,SP) immunohistochemical method to detec the expression of CD 147 and MMP-2 in 20 cases of normal cervical tissue,21 cases of CIN tissue,59 cases of cervical cancer. Analysis of cervical cancer in CD 147 and MMP-2 expression and clinical stage, histological grade and other clinicopathological parameters of relevance,at the same time the relationship between CD 147 and MMP-2 was studyed in the development of cervical cancer for a preliminary study.Results1.CD 147 and MMP-2 were expressed mainly in cancerous lesions,but also expressed in some normal tissues.2.Positive expression rate of CD 147 in normal cervical tissues,CIN,cervical cancer tissues were 30.0%,81.0%,91.5%,the trend has gradually increased(P＜0.05). Among them,significant difference was existed between normal cervical group and CIN group(P＜0.05),also between normal cervical group and cancer group(P＜0.05), CIN group and cancer group(P＜0.05).3.Positive expression rate of MMP-2 in normal cervical tissues,CIN,cervical cancer tissues were 15.0%,38.1%,80.0%,the trend has gradually increased(P＜0.05). Among them,significant difference was existed between normal cervical group and cancer group(P＜0.05),also between CIN group and cancer group(P＜0.05).There was no significant difference between normal cervical group and CIN group (P＞0.05). 4.In cervical carcinoma,positive rate of CD 147 protein expression with lymph node metastasis group was higher than that without lymph node metastasis group (x~2=4.138,P＜0.05);Expression of CD147 in cervical cancer were not related with age,stage,gross type,the degree of differentiation,histological types(P＞0.05).5.In cervical cancer,positive rate of MMP-2 protein’s expression at FIGO stagesⅠ-Ⅱa period was higher than theⅡb-Ⅳperiod(x~2=9.423,P＜0.05),there is lymph node metastasis group was higher than that without lymph node metastasis group(x~2=5.019,P＜0.05);Expression of CD147 in cervical cancer were not related with age,gross type,the degree of differentiation,histological types(P＞0.05).6.The relationship between CD 147 and MMP-2 was positively correlated,and the correlation coefficient rs = 0.283(P＜0.05).Conclusion CD 147 and MMP-2 in the normal cervix,CIN,cervical carcinoma was higher trend;CD 147 in lymph node metastasis is higher than without lymph node metastasis.MMP-2 in the phaseⅡb-Ⅳ,there is lymph node metastasis of cases of cervical cancer is higher than theⅠ-Ⅱa period,no lymph node metastasis;There is synergy between CD 147 and MMP-2;CD 147 and MMP-2 plays an important role in cervical cancer invasion and metastasis,Combined detection of CD 147 and MMP-2 may be a new target of cancer diagnosis and treatment and a new way to assess the severity of cervical cancer.更多还原